BACKGROUND Salvage high-dose chemotherapy (HDCT) along with autologous stem cell transplant (ASCT) plays an important role in the management of patients with germ cell tumors (GCT) and progression after first-line cisplatin-based chemotherapy. In this review, the authors will discuss the history of HDCT as salvage management of patients with GCT, improvement in efficacy and safety over the past 25 years, prognostic factors for outcome, and the conflicting data on the optimal initial salvage approach. METHODS The authors performed a PubMed search of HDCT and GCT to identify articles relevant to this review. After discussion, the articles felt to have contributed most notably to the field were selected for inclusion and summarized. RESULTS Depending on patient selection and timing of HDCT, durable remission rates with salvage HDCT range between 30% and 63%. The combination of carboplatin and etoposide is the standard regimen for the high-dose cycles with more variability in the regimens used for stem cell mobilization. Adding a third agent, particularly an oxazophosphorine (cyclophosphamide and ifosfamide), may add toxicity without increasing efficacy. In addition, sequential (2 or 3 cycle) HDCT regimens appear more effective and safer than single-cycle HDCT regimens. The optimal initial salvage approach (HDCT or conventional-dose chemotherapy) remains an unanswered question and highly controversial. CONCLUSIONS Salvage HDCT with ASCT can cure a significant proportion of patients with GCT and progression after one or more lines of cisplatin-based chemotherapy and thus plays an important role in the contemporary management of high-risk patients.