Nonopsonic phagocytosis mediated by phagocyte receptors that recognize corresponding adhesins on microbial surfaces has attracted increasing interest as a potential host defense mechanism against extracellular pathogens and as a means of survival in the host for intracellular pathogens. Three types of nonopsonic phagocytosis involving carbohydrate-protein interactions (also termed lectinophagocytosis), protein-protein interactions, and hydrophobic interactions are discussed. A prominent receptor on phagocytic cells involved in recognizing pathogens belongs to the CD11/CD18 integrins. It mediates both opsonophagocytosis and nonopsonic phagocytosis and exhibits multiple specificity for different microbial adhesins. In other cases, similar specificity toward a microbial ligand (e.g. the Klebsiella pneumoniae capsule) is shared by dual molecules, one of which (e.g. the mannose-binding protein in serum) mediates opsonophagocytosis and the other (e.g. the macrophage mannose receptor) mediates nonopsonic phagocytosis of the microorganisms. In addition, we discuss how nonopsonic phagocytosis can trigger the phagocytes to release inflammatory agents and cause tissue injury. Further studies of the molecular mechanisms of nonopsonic phagocytosis, in particular those underlying the up-regulation of the phagocytic receptors by various agents, should lead to the development of new approaches for the prevention of infectious diseases.