Differential patterns of gene expression contribute to phenotypic differences between species. Understanding evolutionary changes in gene regulatory elements can help explain traits that separate humans from closely related species. Here, in two separate studies, we investigate gene expression and gene regulatory differences between humans our closest living evolutionary relatives, chimpanzees, in the context of uniquely human traits: increased susceptibility to epithelial cancers and neural developmental and functional processes that underlie our increased cognitive capacity. Using genomic methods to study gene expression and open chromatin, we compare human and chimpanzee responses to a serum challenge, an assay that that mimics patterns of gene expression that occur during cancer progression, and in another approach, we investigate the functional consequences of evolutionary changes in non-coding regulatory elements in neural progenitor cells and neurons. These studies identify recently evolved changes in physiological stress responses in humans, and patterns of adaptive changes in regulatory elements around highly conserved developmental pathways. Together, using these comparative genomic studies in relevant physiological contexts, we can thus further define the molecular basis for uniquely human phenotypes.