Mitotic homologous recombination promotes genome stability through the precise repair of DNA double-strand breaks and other lesions that are encountered during normal cellular metabolism and from exogenous insults. As a result, homologous recombination repair is essential during proliferative stages in development and during somatic cell renewal in adults to protect against cell death and mutagenic outcomes from DNA damage. Mutations in mammalian genes encoding homologous recombination proteins, including BRCA1, BRCA2 and PALB2, are associated with developmental abnormalities and tumorigenesis. Recent advances have provided a clearer understanding of the connections between these proteins and of the key steps of homologous recombination and DNA strand exchange.