Debridement is an essential component of wound bed preparation. Various techniques of debridement are commonly used in clinical practice. This systematic review summarizes and ranks evidence concerning the safety and efficacy of the selective enzymatic debriding agent collagenase. Studies were identified comparing collagenase to inactive (sham) ointment and to alternate techniques for debridement including autolytic and surgical. A preponderance of evidence from this systematic review confirms that collagenase ointment is a safe and effective choice for debridement of cutaneous ulcers and burn wounds.