Mannose-binding lectin (MBL) is an important component of the immune defence able to bind to repeating mannose based structural patterns typical of microbial surface (bacteria, viruses, fungi, parasites) leading to opsonization and phagocytosis, and activation of the complement pathway resulting in lysis of the pathogen. MBL thus plays a very important role in the first line of host immune response. MBL deficiency has been implicated in susceptibility and modulating the severity in viral, bacterial, fungal, and protozoan infections. High MBL levels, on the contrary might be helpful to intracellular organisms, which take the advantage of C3 opsonization and C3 receptor on monocytes/macrophages to enter their host. MBL replacement therapy to help patients with MBL deficiency has undergone phase I clinical trials. Phase II and III trials and production of recombinant MBL for replacement therapy are currently underway.