Abstract Due to its numerous distinctive functions and unique pathology, the human brain, or rather forebrain has been difficult to study in common animal models. Although many basic molecular and cellular events are conserved across species, human brain connectivity, pertinent especially to the cerebral cortex circuitry, is unique and demands extensive research. Despite a great advancement in functional imaging methods accomplished over the last two decades, many basic features of healthy and diseased human forebrain remain elusive. Here we address difficulties in anatomical studies of developing and adult human brain and indicate the new directions and challenges to be addressed in the future. We pay special attention to possibilities of translating animal brain research to human cases. We consider that, although animal experiments play a vital role in understanding fundamental molecular and cellular mechanisms behind brain function, understanding of higher brain functions (language, intelligence, memory) has to be based on understanding uniqueness of human circuitries. Furthermore, brain is the site of many human-specific diseases, such as multiple sclerosis, schizophrenia, and Alzheimer’s disease, for which only partial animal models exist. To study human brain, thus, remains irreplaceable in the quest for new therapeutic tools, as well as in understanding the essence of our being.