The chimpanzee genome sequence is a long-awaited milestone, providing opportunities to explore primate evolution and genetic contributions to human physiology and disease. Humans and chimpanzees shared a common ancestor approximately 5-7 million years ago (Mya). The difference between the two genomes is actually not approximately 1%, but approximately 4%--comprising approximately 35 million single nucleotide differences and approximately 90 Mb of insertions and deletions. The challenge is to identify the many evolutionarily, physiologically, and biomedically important differences scattered throughout these genomes while integrating these data with emerging knowledge about the corresponding "phenomes" and the relevant environmental influences. It is logical to tackle the genetic aspects via both genome-wide analyses and candidate gene studies. Genome-wide surveys could eliminate the majority of genomic sequence differences from consideration, while simultaneously identifying potential targets of opportunity. Meanwhile, candidate gene approaches can be based on such genomic surveys, on genes that may contribute to known differences in phenotypes or disease incidence/severity, or on mutations in the human population that impact unique aspects of the human condition. These two approaches will intersect at many levels and should be considered complementary. We also cite some known genetic differences between humans and great apes, realizing that these likely represent only the tip of the iceberg.