The presence of nodal involvement in penile cancer is the single most important prognostic factor. The first draining lymph nodes (the "first-echelon" or "sentinel" nodes) are invariably within the inguinal lymphatic region. There is no controversy about the need for lymphadenectomy in patients with clinical evident nodal involvement. However, the optimal management of clinically node-negative patients is subject of debate. Removal of nodal metastases at the earliest possible time, preferably in patients with impalpable lymph nodes and microscopic invasion only, improves survival considerably compared with surgical removal at the time when metastases become clinically apparent. Sentinel lymph node biopsy is based on the hypothesis of stepwise distribution of malignant cells in the lymphatic system. The absence of tumor cells in the first lymph node(s) in the lymphatic drainage of the tumor indicates the absence of further spread in regional lymph node basin(s) and is now included in the European Association of Urology guidelines on a suitable therapeutic option on assessing inguinal lymph nodes in penile cancer patients with high-risk features in the primary tumor in the absence of palpable inguinal lymphadenopathy. Minimally invasive surgical approaches to inguinal lymph nodes in penile cancer are still in development requiring further validation in large, multicenter prospective clinical trials. Initial surgical series are however promising. While penile cancer is a rare disease, current research should pave the way to optimizing cancer outcomes while minimizing treatment related morbidity.