Activation-induced cytidine deaminase (AID) instigates mutations and DNA breaks in Ig genes that undergo somatic hypermutation and class switch recombination during B cell activation in response to immunization and infection. This review discusses how AID expression and activity are regulated, including recent discoveries of AID-interacting proteins that might recruit AID to Ig genes, and allow it to target both DNA strands. Also discussed is the accumulating evidence that AID binds to, mutates, and creates breaks at numerous non-Ig sites in the genome, which initiates cell transformation and malignancies.