Each of the human CD1 proteins takes a different route through secretory and endocytic compartments before finally arriving at the cell surface, where these proteins present glycolipid antigens to T cells. Recent studies have shown that adaptor-protein complexes and CD1-associated chaperones control not only CD1 trafficking, but also the development and activation of CD1-restricted T cells. This indicates that CD1 proteins, similar to MHC class I and II molecules, selectively acquire certain antigens in distinct cellular subcompartments. Here, we summarize evidence supporting the hypothesis that CD1 proteins use separate, but parallel, pathways to survey endosomal compartments differentially for lipid antigens.