“I think, therefore I am,” a famous dictum attributed to the 17th century philosopher René Descartes, is deceptively simple, yet the biology at the heart of it is so overwhelmingly complex that it boggles the mind. Cognitive thought is a fundamental aspect of human existence, and the neural underpinnings of this fascinating ability have captivated inquisitive minds for centuries. In this exciting age of modern neuroscience, great progress is being made in understanding the neurobiology of thought from cellular, molecular, developmental, evolutionary, and systems neuroscience perspectives. The brain is often considered the most complex organ. Within the brain, the cerebral cortex is the region responsible for higher thought processes. The building of the cerebral cortex is an intricate process requiring a beautifully orchestrated program where billions of neurons are generated and assembled into complex circuits at the right time and place and with the right functional specializations. While much has been learned about mammalian neurogenesis and cortex development from rodent models, there are fundamental differences between mice and humans that have made understanding uniquely human cognitive abilities challenging. The human cerebral cortex is characterized by two unique features: its unusual size relative not only to the rest of the brain, but also to overall body size, as well as its level of gyrification, or cortical folding, which is thought to increase surface area. Both of these aspects are thought to be important for higher human cognitive abilities. These limitations have prompted researchers to look beyond the mouse to understand the mechanisms at play allowing for expanded cerebral cortex size. In the past few years, our cellular and molecular understanding of human cerebral cortical neuron diversity and development has blossomed. With advances in single-cell analysis and the use of cerebral organoids, the ability to study this tissue type has become less of a barrier. A recent study from Xiaoqun Wang and colleagues utilized single-cell RNA sequencing of the developing prefrontal cortex to paint a picture of the action during early human brain development (Zhong et al., 2018Zhong S. Zhang S. Fan X. Wu Q. Yan L. Dong J. Zhang H. Li L. Sun L. Pan N. et al.A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex.Nature. 2018; 555: 524-528Crossref PubMed Scopus (323) Google Scholar). By sequencing over 2,300 cells across gestational ages 8 to 26 weeks, Zhong and colleagues not only identified numerous cell subtypes, but also tracked their developmental trajectories. Such information can serve as an important reference for understanding this critical window of neurogenesis in an area of the brain that is centrally involved in complex cognitive functions, such as personality, decision making, social behavior, and planning. Single-cell gene expression analysis from fetal cortical tissues focused on the ventricular zone and subventricular zone has also provided insights into the neural stem cell niches that give rise to the neocortex and suggest how the niche supports the expansion of the human neocortex (Pollen et al., 2015Pollen A.A. Nowakowski T.J. Chen J. Retallack H. Sandoval-Espinosa C. Nicholas C.R. Shuga J. Liu S.J. Oldham M.C. Diaz A. et al.Molecular identity of human outer radial glia during cortical development.Cell. 2015; 163: 55-67Abstract Full Text Full Text PDF PubMed Scopus (477) Google Scholar). In a study published earlier this year, Geschwind and colleagues took on mapping the gene regulatory elements involved in human cortex development (de la Torre-Ubieta et al., 2018de la Torre-Ubieta L. Stein J.L. Won H. Opland C.K. Liang D. Lu D. Geschwind D.H. The Dynamic Landscape of Open Chromatin during Human Cortical Neurogenesis.Cell. 2018; 172: 289-304.e18Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar). Integrating chromatin accessibility, chromatin interactions, and gene expression, they identified distal regulatory regions and found that human-gained enhancers preferentially exert control over genes expressed in outer radial glia, neural stem cells that are expanded in humans and are of particular interest in the context of neocortex expansion. By further integrating their findings with genome-wide association studies, de la Torre-Ubieta et al. connect common genetic variants associated with a number of psychiatric disorders and cognitive function with their set of cortical neurogenesis regulatory elements. While advances have been made in mining incredible amounts of molecular information from rare and precious human embryonic samples, the use of human cerebral organoids as models for cortical development is paving a path for researchers to probe human-specific neurodevelopmental questions (Lancaster et al., 2013Lancaster M.A. Renner M. Martin C.A. Wenzel D. Bicknell L.S. Hurles M.E. Homfray T. Penninger J.M. Jackson A.P. Knoblich J.A. Cerebral organoids model human brain development and microcephaly.Nature. 2013; 501: 373-379Crossref PubMed Scopus (2772) Google Scholar, Camp et al., 2015Camp J.G. Badsha F. Florio M. Kanton S. Gerber T. Wilsch-Bräuninger M. Lewitus E. Sykes A. Hevers W. Lancaster M. et al.Human cerebral organoids recapitulate gene expression programs of fetal neocortex development.Proc. Natl. Acad. Sci. USA. 2015; 112: 15672-15677Crossref PubMed Scopus (89) Google Scholar, Quadrato et al., 2017Quadrato G. Nguyen T. Macosko E.Z. Sherwood J.L. Min Yang S. Berger D.R. Maria N. Scholvin J. Goldman M. Kinney J.P. et al.Cell diversity and network dynamics in photosensitive human brain organoids.Nature. 2017; 545: 48-53Crossref PubMed Scopus (645) Google Scholar) and also to study specific diseases such as Miller-Dieker syndrome, a severe form of lissencephaly (Bershteyn et al., 2017Bershteyn M. Nowakowski T.J. Pollen A.A. Di Lullo E. Nene A. Wynshaw-Boris A. Kriegstein A.R. Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia.Cell Stem Cell. 2017; 20: 435-449.e4Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar, Iefremova et al., 2017Iefremova V. Manikakis G. Krefft O. Jabali A. Weynans K. Wilkens R. Marsoner F. Brändl B. Müller F.J. Koch P. Ladewig J. An Organoid-Based Model of Cortical Development Identifies Non-Cell-Autonomous Defects in Wnt Signaling Contributing to Miller-Dieker Syndrome.Cell Rep. 2017; 19: 50-59Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar). While mice may fall short in terms of modeling certain features of human cortical development, ferrets are proving to provide an attractive alternative. Because ferrets not only have cortical surface morphologies more similar to humans, but also a larger cortex and a higher diversity of neural progenitors, studies of gene function during neurogenesis in ferrets seem to more accurately reflect their potential functions in humans. An interesting example of this comes from a new study from Walsh, Bae, and colleagues (Johnson et al., 2018Johnson M.B. Sun X. Kodani A. Borges-Monroy R. Girskis K.M. Ryu S.C. Wang P.P. Patel K. Gonzalez D.M. Woo Y.M. et al.Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size.Nature. 2018; 556: 370-375Crossref PubMed Scopus (92) Google Scholar). By disrupting in ferrets a gene called ASPM—a very common recessive microcephaly gene whose disruption in mice has little consequence—they not only recapitulated the severe microcephaly seen in humans, but could also pinpoint the neurodevelopmental dysfunction to a premature movement of a population of neural progenitor cells that are absent in mice. Moving forward, it will be thought provoking to see how clever applications of these technologies not only push forward our understanding of human cognitive abilities, but also illuminate the etiology behind a whole host of neurodevelopment disorders.