The macrophage mannose receptor (MR, CD206) is a C-type lectin expressed predominantly by most tissue macrophages, dendritic cells and specific lymphatic or endothelial cells. It functions in endocytosis and phagocytosis, and plays an important role in immune homeostasis by scavenging unwanted mannoglycoproteins. More attention is being paid to its particularly high expression in tissue pathology sites during disease such the tumor microenvironment. The MR recognizes a variety of microorganisms by their mannan-coated cell wall, which is exploited by adapted intracellular pathogens such as Mycobacterium tuberculosis, for their own survival. Despite the continued development of drug delivery technologies, the targeting of agents to immune cells, especially macrophages, for effective diagnosis and treatment of chronic infectious diseases has not been addressed adequately. In this regard, strategies that optimize MR-mediated uptake by macrophages in target tissues during infection are becoming an attractive approach. We review important progress in this area.