The following is an update to a book entitled, “A Historical Review of Enzymatic Debridement: Revisited”, which I wrote in 2003. Since its publication, while the relevant clinical evidence has remained consistent, the amount of biochemical research and knowledge gained has been impressive. In the first chapter a sampling of the typical topical enzymatic debriding agents that have been used in wound care are reviewed and interestingly enough only one remains on the market. The FDA has removed all others from the marketplace and an explanation is provided in chapter one along with descriptions of the use and mode of action (MoA) of these agents. Chapter two is a review of the many different types of collagen found in the body, including their structure, form, and function as so much additional insight into this molecule has been gained since 2003. In chapter three we see an account depicting the many advances in understanding matrix metalloproteinases (MMPs) reviewed in detail. Form, function, tissue orientation and preferred substrates are addressed. Finally, in chapter four we see the history of the MoA of MMPs as compared to bacterial collagenase starting in the early ‘80s to the time of this current publication. In addition we see the level of complexity of bacterial collagenases compared to MMPs, helping us to better understand why bacterial collagenase is much more efficient at removing necrotic tissue from wounds than are our own (endogenous) MMPs. I hope the reader finds this review useful from an academic standpoint, but more importantly from a clinical framework helping to understand the role of these types of therapies in wound care.