Cellular immunity mediated via major histocompatibility complex class I (MHC class I) antigen presentation is central to the clearance of intracellular pathogens and cancer cells from the body. MHC class I molecules are comprised of a heavy chain, a light chain (β2-microglobulin or β2m), and an 8–11-mer peptide. Proteins within the cell are processed into peptides, followed by loading of peptides onto MHC class I complexes with the combined action of several endoplasmic reticulum (ER)-resident chaperones [1]. Although the assembly conditions in the canonical ER pathway are finely tuned, MHC class I molecules traffic through many subcellular locations, including the Golgi apparatus, the plasma membrane, and endolysosomes. The endolysosomes in particular are important during the later half of the MHC class I life cycle, as MHC class I molecules constitutively recycle between the endosomes and the plasma membrane [2]. Endosomes could function as a secondary compartment for assembly, following the ER egress of MHC class I molecules. The ability of MHC class I molecules to assemble with peptide in endosomes is a significant area of interest, as the endosomal system does not generally contain ER chaperones that are essential for the assembly of several MHC class I allotypes in the ER. In this review, we will discuss the current evidence for endosomal assembly of MHC class I, as well as open questions for the field related to this unconventional mode of assembly.