The stable assembly of Major Histocompatibility Complex (MHC) molecules with peptides is controlled by a number of cofactors, including proteins with general housekeeping functions and proteins with dedicated functions in MHC assembly. Recent work in my laboratory has focused on two chaperones, tapasin (tpn) and DM, that play critical roles in the loading of peptides onto MHC class I and MHC class II molecules, respectively. Tapasin is a transmembrane protein that tethers empty class I molecules in the endoplasmic reticulum to the transporter associated with antigen processing. DM is a peptide exchange factor that binds with empty and peptide-loaded class II molecules in endosomal and lysosomal compartments. Although a number of different functions for tapasin and DM have been proposed, emerging evidence suggests that both of these chaperones retain unstable MHC molecules in peptide-loading compartments until they bind with high-affinity peptides. These cofactors therefore promote the surface expression of long-lived MHC-peptide complexes.