Immunoglobulin (Ig) class switch recombination (CSR) is the process occurring in mature B cells that diversifies the effector component of antibody responses. CSR is initiated by the activity of the B cell-specific enzyme activation-induced cytidine deaminase (AID), which leads to the formation of programmed DNA double-strand breaks (DSBs) at the Ig heavy chain (Igh) locus. Mature B cells use a multilayered and complex regulatory framework to ensure that AID-induced DNA breaks are channeled into productive repair reactions leading to CSR, and to avoid aberrant repair events causing lymphomagenic chromosomal translocations. Here, we review the DNA repair pathways acting on AID-induced DSBs and their functional interplay, with a particular focus on the latest developments in their molecular composition and mechanistic regulation. Mature B cells rely on a multilayered regulatory framework to ensure that S region DSBs are preferentially channeled into the NHEJ pathway.The structure of AID-induced breaks influences both the DSB end-processing mode and end-joining pathway choice.Both the SSA factor RAD52 and the A-EJ protein HMCES contribute strand pairing activities during repair of S region DSBs.Repair of AID-initiated breaks is influenced by Igh locus-specific organizational features that ensure productive end-joining events leading to CSR. 53BP1 contributes both structural and resection modulatory roles to the regulation of CSR repair outcomes.Shieldin and CST complexes are 53BP1 and Rif1 downstream effectors, and actively counteract the processing of S region DSBs into ssDNA by combining inhibition of DNA end resection and limited fill-in synthesis of resected tracks.