Dupuytren's contracture is a benign fibromatosis of the palmar and digital fascia of the hand of uncertain etiology, resulting in nodules and cords beneath the skin of the palm of the hands that may lead to the development of contractures. Surgical intervention is often considered when metacarpophalangeal (MP) joint contracture is 30° or more, or when there is any degree of proximal interphalangeal (PIP) joint contracture. Collagenase clostridium histolyticum (CCH) is a nonsurgical, minimally invasive enzymatic drug indicated for the treatment of adult patients with Dupuytren's contracture (DC) and palpable cord. CCH has been available for approximately 3.5 years, and postapproval experience indicates that the effectiveness of CCH is equivalent to or better than efficacy observed in clinical trials, as seen by lower injection rates to achieve clinical success. Postapproval experience has shown a risk-benefit profile that favors CCH for patients not indicated for surgery based on current recommendations and shows also that treating earlier-stage vs later-stage joint contracture results in significantly better outcomes on average. Postapproval surveillance reveals a safety profile similar to that observed in clinical trials. Nonserious adverse events are mainly local reactions; tendon rupture, a serious adverse event, is reported rarely in the clinical practice setting and at a lower rate than in clinical trials. Risk Evaluation and Mitigation Strategy (REMS) training is designed to mitigate benefit vs risk to achieve safe and effective use of CCH.