Successful topical treatment of chronic wounds requires adequate debridement, bacterial balance, and moisture balance. Wound dressings are widely used for controlling wound bioburden and managing wound exudate. Frequently, they are used in combination with other topical therapeutic drugs, such as enzymatic debriding agents for the removal of wound necrotic tissues. Such combinations may allow several treatment objectives to be addressed simultaneously, including exudate and bioburden management, debridement, and tissue regeneration. In order to understand the compatibility between debriding enzymes and commonly used dressings, extracts of silver dressingsa, iodine dressingsb, a pigment-complexed PVA dressingc, and a collagen dressingd, have been examined in vitro with collagenase, the active ingredient in the only FDA approved enzymatic debriding ointmente. The results demonstrated that the pigment-complexed PVA dressing and the collagen dressing were compatible with collagenase, while the iodine dressings inhibited the activity of collagenase. The ionic silver dressing tested showed some low inhibition, while the nano-crystal silver dressing caused more than a 50% decrease in collagenase activity. In addition, a moisturized environment has been found to be favorable for the debriding ointment compared with a dry application. These results demonstrate that the debridement action of collagenase can be affected by certain wound dressings. Appropriate selection of a wound dressing will ensure optimal debridement efficacy of a collagenase debriding agent.