Mannose-binding lectin (MBL) is an important element of the innate immune defence system. The protein binds to the sugars present on many microbial surfaces and subsequently activates the complement system through a family of specific proteases called the MASPs (MBL-associated serine proteases). Studies of MBL binding to selected Gram-negative organisms suggest that the lipopolysaccharide (LPS) structure is of primary importance. For a range of clinically relevant organisms MBL binding leads to activation and cleavage of C4 and C3, suggesting that this is a major pathway for opsonophagocytosis. MBL deficiency, resulting from three mutations in exon 1 and polymorphisms in the promoter region of the gene, is associated with both increased susceptibility to infections and autoimmune disease. Recent evidence indicates that the protein also modulates disease severity, possibly by influencing cytokine production.