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ABSTRACT Introduction Current clinical guidelines on Peyronie’s disease (PD) advocate non-surgical treatment options as the first-line therapy despite inconsistent clinical outcomes when compared to definitive penile reconstructive surgery. Areas covered This article examines the current understanding of established contemporary and emerging pharmacotherapies for PD. Emphasis has been placed on published clinical studies on drugs in the last 10 years. Expert opinion Published studies have shown that combination therapy is likely more effective than monotherapy. Combined treatment modalities involving various oral and/or intralesional pharmacotherapies together with mechanical devices or clinical psychosexual therapy may provide additional or synergistic benefits for PD patients. A multidisciplinary approach coupled with more novel targets for pharmacological intervention could deliver a more effective treatment paradigm to prevent or at least delay the need for definitive penile reconstructive surgery. Drugs targeting the inhibition of TGF-β1 pathway and myofibroblast transformation are of great interest and studies into next-generation genetic sequencing and transcriptional biomarker regulatory pathways in PD will provide useful insights into the pathophysiology of PD, and assist the development of future regenerative technology including cellular-based therapies to target various anti-fibrotic molecular mechanisms and the potential to be integrated into existing treatment armamentarium for PD.