Peptide binding to MHC class I molecules is a component of a folding and assembly process that occurs in the endoplasmic reticulum (ER) and uses both cellular chaperones and dedicated factors. The involvement of glycoprotein quality-control chaperones and cellular oxidoreductases in peptide binding has led to models that are gradually being refined. Some aspects of the peptide loading process (e.g., the biosynthesis and degradation of MHC class I complexes) conform to models of glycoprotein quality control, but other aspects (e.g., the formation of a stable disulfide-linked dimer between tapasin and ERp57) deviate from models of chaperone and oxidoreductase function. Here we review what is known about the intersection of glycoprotein folding, oxidative reactions, and MHC class I peptide loading, emphasizing events that occur in the ER and within the MHC class I peptide loading complex.