Mannose-binding lectin (MBL; also known as mannan-binding lectin) is involved in first-line defence by binding to bacteria, viruses, protozoa and helminths through a pattern-recognition mode of detection and then initiating a range of host responses. Currently, we have been unable to extrapolate from what we know of the biochemistry of MBL binding to predict accurately the interaction of MBL with individual micro-organisms; even subtle surface alterations have been shown to have an extensive impact on MBL-mediated recognition of pathogens. MBL has a major protective effect through activation of the complement system via MBL-associated serine proteases (MASPs). This can cause the lysis of Gram-negative bacteria and also opsonize a wide spectrum of potential pathogens for phagocytosis. MBL may also influence phagocytosis in the absence of complement activation through an interaction with one or more collectin receptors. This may also be the basis for a direct effect of the protein on inflammatory responses. MBL can alter the function of microbial structures, such as gp120 of HIV, to prevent infection. The protein may also interact with the components of other cascade systems such as the clotting system, which will have a role in microbial pathogenesis. An understanding of these basic mechanisms will be vital if we are to use purified or recombinant MBL in therapeutic applications.