Homologous recombination (HR) is a critical process that repairs DNA double-stranded breaks (DSBs) and interstrand crosslinks (ICLs), and supports DNA replication in the recovery of stalled or broken replication forks. The central core of proteins, primarily the RecA homolog Rad51, catalyzes key reactions such as homology search and DNA strand invasion. Context-specific factors, including the tumor suppressor protein BRCA2, play crucial roles in HR and are essential for maintaining genome stability and tumor suppression. HR mechanisms are diverse and involve multiple pathways, including synthesis-dependent strand annealing (SDSA), break-induced replication (BIR), and double-strand break repair (DSBR). These pathways differ in their processing of DSBs, assembly of the Rad51 filament, and resolution of the D-loop intermediate. HR also supports replication fork stability by facilitating gap repair and the resolution of one-sided DSBs. In ICL repair, HR collaborates with nucleotide excision repair (NER) and involves the formation of a single Holliday junction. The complex web of pathways supporting stalled or broken replication forks includes translesion DNA synthesis (TLS), template switching by fork regression, and HR. Context-specific factors, such as the Mus81-Mms4 complex, are essential for HR during replication fork support but may have limited roles in DSB repair. The Fanconi Anemia (FA) pathway, unique to mammals, is critical for ICL repair and involves the recruitment of Rad51-mediated HR. Overall, HR is a multifaceted process that integrates DNA repair and replication, and its dysfunction can lead to genomic instability and cancer predisposition.Homologous recombination (HR) is a critical process that repairs DNA double-stranded breaks (DSBs) and interstrand crosslinks (ICLs), and supports DNA replication in the recovery of stalled or broken replication forks. The central core of proteins, primarily the RecA homolog Rad51, catalyzes key reactions such as homology search and DNA strand invasion. Context-specific factors, including the tumor suppressor protein BRCA2, play crucial roles in HR and are essential for maintaining genome stability and tumor suppression. HR mechanisms are diverse and involve multiple pathways, including synthesis-dependent strand annealing (SDSA), break-induced replication (BIR), and double-strand break repair (DSBR). These pathways differ in their processing of DSBs, assembly of the Rad51 filament, and resolution of the D-loop intermediate. HR also supports replication fork stability by facilitating gap repair and the resolution of one-sided DSBs. In ICL repair, HR collaborates with nucleotide excision repair (NER) and involves the formation of a single Holliday junction. The complex web of pathways supporting stalled or broken replication forks includes translesion DNA synthesis (TLS), template switching by fork regression, and HR. Context-specific factors, such as the Mus81-Mms4 complex, are essential for HR during replication fork support but may have limited roles in DSB repair. The Fanconi Anemia (FA) pathway, unique to mammals, is critical for ICL repair and involves the recruitment of Rad51-mediated HR. Overall, HR is a multifaceted process that integrates DNA repair and replication, and its dysfunction can lead to genomic instability and cancer predisposition.