Although debridement is an essential part of wound care, information to guide evidence-based decisions is limited in the literature. Assuming studies to ascertain the effectiveness of pharmaceutically based enzymatic debridement products are more prolific than studies using nonpharmaceutical debridement options, a literature review was conducted to provide an evidence base to justify current wound care practice. Information on collagenase- and papain-urea-based products was reviewed with emphasis on their functional components, mechanisms of action, and patient considerations. The Medline Database, Cochrane Database of Systematic Reviews, InfoPOEMs, Institute for Clinical Systems Improvement, National Guideline Clearinghouse, and Primary Care Clinical Practice Guidelines were searched for documents published between 1967 and 2007 using the following terms: enzymatic debridement, collagenase, papain-urea, papain-urea chlorophyllin copper complex, wounds, and diabetic foot wounds. Sixteen of of 44 relevant citations obtained fit the established criteria for readability, accuracy, reliability and validity of information. Four of the 16 studies included a control treatment, the external validity of 13 studies was limited due to small sample size, and only four studies reported a statistically significant difference in treatment outcome. Predicted bias and publication bias were common. Of the studies detailed herein, three qualified as A level, 13 qualified as B level, and none were considered to provide C level evidence. Although clinicians can glean practical information from the homogenized findings regarding patient demographics, wound type, and therapeutic goals, future studies designed to meet the criteria of level A evidence are needed to provide evidence for the use of enzymatic debridement agents.