Proteolytic enzymes are a family of proteins that serve to degrade necrotic debris derived from cell breakdown. They are produced endogenously often as precursor proteins whose activation is precisely regulated. These activated enzymes serve many functions in normal as well as pathological situations. In particular they are involved in the regulation of cell maturation and multiplication; collagen synthesis and turnover; the development and removal of the perivascular fibrin cuffs found in venous insufficiency and leg ulceration as well as the removal of dead tissues following inflammation. As a limited number of enzymes perform all these functions, it is difficult to predict the effects of applying synthetic proteolytic enzymes to a wound. Many such enzymes are currently commercially available and being promoted as alternatives to surgical wound debridement. It is important for their use to be considered in the context of their interaction with endogenous proteases, their physiological role in tissue, their ability to reach a desired target and the stage of wound healing at the time they are applied.