In eukaryotes, DNA is exchanged between endosymbiosis-derived compartments (mitochondria and chloroplasts) and the nucleus. Organelle-to-nucleus DNA transfer involves repair of double-stranded breaks by nonhomologous end-joining, and resulted during early organelle evolution in massive relocation of organelle genes to the nucleus. A large fraction of the products of the nuclear genes so acquired are retargeted to their ancestral compartment; many others now function in new subcellular locations. Almost all present-day nuclear transfers of mitochondrial or plastid DNA give rise to noncoding sequences, dubbed nuclear mitochondrial DNAs (NUMTs) and nuclear plastid DNAs (NUPTs). Some of these sequences were recruited as exons, thus introducing new coding sequences into preexisting nuclear genes by a novel mechanism. In organisms derived from secondary or tertiary endosymbiosis, serial gene transfers involving nucleus-to-nucleus migration of DNA have also occurred. Intercompartmental DNA transfer therefore represents a significant driving force for gene and genome evolution, relocating and refashioning genes and contributing to genetic diversity.