The cornerstone of Charles Darwin's theory of evolution is the vertical inheritance of traits from parent to offspring across successive generations. However, molecular evolutionary biologists have shown that extensive horizontal (also known as lateral) gene transfer (HGT) can occur between distantly related species. Comparative sequence analyses of genomes indicates that the universal tree of life might be at risk because of pervasive, ancient HGT. Considerable debate now ensues about the role of HGT in genome evolution. At stake are a fundamental understanding of how life evolved and a deeper knowledge of the functioning of all genomes, including that of humans.