C-type lectin receptors (CLRs) are a family of transmembrane proteins having at least one C-type lectin-like domain (CTLD) on the cell surface and either a short intracellular signaling tail or a transmembrane domain that facilitates interaction with a second protein, often the Fc receptor common gamma chain (FcRγ), that mediates signaling. Many CLRs directly recognize microbial cell walls and influence innate immunity by activating inflammatory and antimicrobial responses in phagocytes. In this review, we examine the contributions of certain CLRs to activation and regulation of phagocytosis in cells such as macrophages, dendritic cells and neutrophils.