It has been hypothesized that one of the consequences of the highly evolved cognitive capacity of the human brain is the development of increased vulnerability to cognitive disorders. Technical breakthroughs in genomics have allowed us to begin to identify genetic and molecular signatures in the central nervous system that distinguish humans from non-human primates. We have identified novel human-specific patterns of gene expression and regulation in the neocortex. These data suggest that the human brain has undergone rapid modifications of gene expression patterns to support our enhanced cognitive abilities. We have carried out functional follow up of a number of these genes with human-specific co-expression patterns, focusing on genes that regulate transcription and/or mRNA splicing. These data have uncovered additional gene co-expression patterns and molecular pathways that might be involved in human disorders of cognition. We have also shown that human brain gene expression data can be harnessed to provide insight into active human brain states, identifying genes associated with cognitive disorders. For example, genes that have differential correlation with human brain activity in the resting state in patients with autism would strengthen the importance of altered functional connectivity in autism pathophysiology as a consequence of disrupted gene expression networks. Together, these approaches are providing functional confirmation of the genetic basis of cognition and cognitive disorders.