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Penile cancer is a rare malignancy, most commonly diagnosed in older men, associated with poor outcomes, dramatic decline in quality of life and sexual function. Squamous cell carcinoma is the most common histopathology of penile cancer, accounting for 95% of all cases. Localized, early-stage penile cancer can be effectively managed through penile-sparing techniques in many cases, though advanced stages of penile cancer carry a poor prognosis. Current innovative treatments are exploring the role of targeted therapy, HPV-directed therapy, immune checkpoint inhibitors and adoptive T-cell therapies in treatment and prevention of relapse of penile cancer. Clinical trials are investigating the potential of targeted therapies and immune checkpoint inhibitors in advanced penile cancer. This review examines the current management of penile cancer and highlights future directions in research and treatment., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 White et al.)