The shuttling of substrates across a cellular membrane frequently requires a specialized ATP-binding cassette (ABC) transporter, which couples the energy of ATP binding and hydrolysis to substrate transport. Due to its importance in immunity, the ABC transporter associated with antigen processing (TAP) has been studied extensively and is an excellent model for other ABC transporters. The TAP protein pumps cytosolic peptides into the endoplasmic reticulum for loading onto class I major histocompatibility complex (MHC) for subsequent immune surveillance. Here, we outline a potential mechanism for the TAP protein with supporting evidence from bacterial transporter structures. The similarities and differences between TAP and other transporters support the notion that ABC transporters in general have adapted around a universal transport mechanism.—Procko, E., O'Mara, M. L., Bennett, W. F. D., Tieleman, D. P., Gaudet, R. The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter.