The intention of treatment in germ cell cancer remains curative, even if metastatic disease is present. The backbone of systemic treatment in metastatic germ cell cancer is built on platinum-based combination chemotherapy regimens, resulting in 5-year overall survival rates of up to 95% in the International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis group and 67% in the poor prognosis group. Also, in nonmetastasized, clinical stage I germ cell cancer, adjuvant platinum-based chemotherapy is an option for selected patients, when risk factors are present, or if patients are not willing to undergo active surveillance. Here, we review indications and options concerning systemic treatment in localized as well as in synchronous metastatic or relapsed germ cell cancer. Furthermore, we provide an overview of multiple treatment options in refractory disease as well as in the palliative treatment setting. Due to the favorable outcome, an adequate and timely administration of systemic treatment is of utmost importance, as careful monitoring for long-term toxicity after chemotherapy is essential in the follow-up setting.