Metalloproteinases play an important role in the poisoning process by snake venoms. They evoke systemic injury, by degrading or activating host blood factors, and local damage by acting on endothelial cell surface proteins. Plasma and/or muscle of venomous and non-venomous snakes as well as of some special mammals possess metalloproteinase inhibitors that behave as soluble acceptors available for a rapid inhibition of the deleterious action of these enzymes. The purpose of this review is to describe the state of the art on natural immunity against snake venom metalloproteinases and to overview this field by discussing the available structural and biological properties of the inhibitors protein/gene families.