Why do genetic disease risks vary across the globe? Did our ancestors mate with Neanderthals? How healthy were ancient humans? The answers to these questions can be found in the genomes of ancient and modern humans. The complex histories of our ancestors are written in DNA and natural selection contributes to differences in disease risks across populations. There is genetic evidence that some of our ancestors mated with Neanderthals, Denisovans, and other unknown “ghost” populations. These ancient couplings are relevant to human health, as having large amounts of Neanderthal DNA increases the likelihood neurological disorders. Intriguingly, genomic medicine approaches can be applied to ancient samples – even when remains are incomplete. On a broad scale, genetic disease risks are similar for ancient and modern humans. However, individuals who lived in the recent past appear to have been healthier than individuals who lived in the deep past. Disease risks are not constant, they continue to evolve. Just as medicine benefits from knowledge of family history, so too can public health genomics benefit from knowledge of our species’ history.