The escape and migration of genetic information between mitochondria, chloroplasts, and nuclei have been an integral part of evolution and has a continuing impact on the biology of cells. The evolutionary transfer of functional genes and fragments of genes from chloroplasts to mitochondria, from chloroplasts to nuclei, and from mitochondria to nuclei has been documented for numerous organisms. Most documented instances of genetic material transfer have involved the transfer of information from mitochondria and chloroplasts to the nucleus. The pathways for the escape of DNA from organelles may include transient breaches in organellar membranes during fusion and/or budding processes, terminal degradation of organelles by autophagy coupled with the subsequent release of nucleic acids to the cytoplasm, illicit use of nucleic acid or protein import machinery, or fusion between heterotypic membranes. Some or all of these pathways may lead to the escape of DNA or RNA from organellar compartments with subsequent uptake of nucleic acids from the cytoplasm into the nucleus. Investigations into the escape of DNA from mitochondria in yeast have shown the rate of escape for gene-sized fragments of DNA from mitochondria and its subsequent migration to the nucleus to be roughly equivalent to the rate of spontaneous mutation of nuclear genes. Smaller fragments of mitochondrial DNA may appear in the nucleus even more frequently. Mutations of nuclear genes that define gene products important in controlling the rate of DNA escape from mitochondria in yeast also have been described. The escape of genetic material from mitochondria and chloroplasts has clearly had an impact on nuclear genetic organization throughout evolution and may also affect cellular metabolic processes.