The MR is a highly effective endocytic receptor with a broad binding specificity encompassing ligands of microbial and endogenous origin and a poorly characterized ability to modulate cellular activation. This review provides an update of the latest developments in the field. It discusses how MR biology might be affected by glycosylation and proteolytic processing, MR involvement in antigen delivery, and the potential contribution of MR to T cell differentiation and cellular activation. Further understanding of these areas will, no doubt, inform the design of novel, therapeutic tools for improved vaccination, control of inflammation, and tumor chemotherapy, which will benefit from exploiting MR-efficient internalization properties and unique pattern of expression.