Commercially available collagenase clostridium histolyticum (CCH) comprises a mixture of clostridial type-I/II collagenase enzymes, which enzymatically destroy collagen deposits. CCH is currently approved in the USA, EU and Canada for the treatment of Dupuytren’s contracture with a palpable cord in the hands of adult patients. Intralesional injection of CCH has demonstrated safety and efficacy in the treatment of Peyronie’s disease (PD) in Phase I–III clinical trials. Improvement of penile curvature deformity and psychological symptoms (degree of patient bother associated with PD) has been achieved among patients with PD. CCH is safe and well tolerated, with adverse events localized to the injection site. This article reviews the potential mechanism of action and summarizes the clinical experience with CCH in patients with PD.