The majority of patients with germ cell tumors who fail first-line treatment will still be cured. Patients without first-line chemotherapy who fail surveillance, radiotherapy, or surgery will be managed according to the treatment algorithms of their primary metastatic disease. These patients usually receive three to four cycles of cisplatin, etoposide, and bleomycin.Salvage treatment of patients who relapse after first-line chemotherapy is more complex and requires an experienced and highly specialized team. Two distinct treatment strategies can be pursued: four cycles of conventional-dose chemotherapy with cisplatin, ifosfamide, and either etoposide, paclitaxel, or vinblastine; or early intensification of first-salvage treatment using sequential high-dose chemotherapy. Salvage surgery is frequently required after completion of salvage chemotherapy to completely resect all radiologic residual manifestations. Patients with brain metastases should receive upfront whole brain radiation concurrent with salvage chemotherapy. Patients with late relapses more than 2 years after first-line treatment should receive immediate salvage surgery whenever this is technically feasible.