The American cockroach Periplaneta americana has been a model organism for biochemical and physiological study for almost a century, however, its use does not benefit from the genetic tools found in key model species such as Drosophila. To facilitate the use of the cockroach as a model system in neuroscience, and to serve as a foundation for functional and translational experimentation, a transcriptome of the cephalic ganglia was generated and annotated. The transcriptome of the cerebral and gnathic ganglia of the cockroach was assembled and differential expression profiles between these ganglia were generated. The transcriptome assembly yielded >400k transcripts, with >40k putative coding sequences. Gene ontology and protein domain searches indicate the cerebral and gnathal ganglia have distinct genetic expression profiles, while on the other hand none of the >100 identified GPCRs were differentially expressed. The developmental Toll signaling pathway appears to be active in the adult CNS, which may suggest a separate role for this pathway besides innate immune activation or embryonic development. The catabolic glycolytic and citric acid cycle enzymes are well represented in both ganglia, but key enzymes are more highly expressed in the gnathal ganglia. Both ganglia express gluconeogenic and trehaloneogenic enzymes suggesting a larger role of the CNS in regulating hemolymph‐sugar homeostasis than previously appreciated. Several homologs of proteins involved in synaptic plasticity and neurodegenerative diseases are also present. The annotation and quantification of the cephalic ganglia transcriptome reveal both canonical and novel pathways in signaling and metabolism in an adult insect and lay a foundation for future functional and genetic analysis. Additionally, the presence of homologs whose mutations are known to be critical in human nervous systems diseases may allow for adaptation from Drosophilaand mouse models, opening new avenues for experimentation into disease processes and pharmacology. These results shed light on the signaling and metabolic pathways of the cockroach brain and may expand of the role of the cockroach as a model system in neuroscience research.