Penile Intraepithelial Neoplasia (PeIN) is the precursor lesion of penile squamous cell carcinoma (SCC). Topical therapies are a non-invasive first line option for the treatment of biopsy-proven PeIN. Treatment of stage 0 PeIN with 5-Fluorouracil and imiquimod is recommended due to the high morbidity and mortality associated with progression to SCC. Despite treatment, approximately 2.6–13% will progress to SCC, necessitating close surveillance. Stage III and IV penile cancer, with nodal or metastatic disease, may be treated with systemic chemotherapy in combination with other therapeutic modalities such as surgery or radiation therapy.