Novel paradigms are emerging in the field of IgE regulation. Gene-environment interactions are increasingly considered to be major determinants of the type and amplitude of allergen-induced antibody responses. At the molecular level, the mechanistic connection between transcription and switching has been strengthened by the recent discovery that class switch recombination requires activation-induced deaminase, a novel RNA editing enzyme. These findings will be critical for our understanding of the mechanisms that determine immunoglobulin isotype expression during immune responses.