Class-switch recombination (CSR) occurs by an unusual and intriguing mechanism that has not been clearly elucidated as yet. Currently, we know that this mechanism involves recombination between large and highly repetitive switch (S) regions, is targeted by S-region transcription and requires the activity of the newly discovered activation-induced deaminase (AID). In this review, we discuss the potential role of these factors in CSR, discuss potential relationships between CSR and somatic hypermutation, and speculate how CSR and related mechanisms might contribute to genomic instability.