Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world, and survival rates for advanced disease remain low with standard platinum-based chemotherapy. One treatment strategy that has been investigated extensively in NSCLC is that of "maintenance" therapy. Options for maintenance include maintaining response to initial therapy by continuing the initial combination chemotherapy regimen, continuing only single agent chemotherapy, or by introducing a new agent. Treatments that have been studied in randomized trials to date include chemotherapy, molecularly targeted agents, and immunotherapy approaches. After the development of multiple new agents that show activity in NSCLC and have a tolerable side effect profile, there has been increasing interest recently in this treatment strategy. In this study, we examine the evolution of this strategy by reviewing trials investigating the main treatment paradigms used in maintenance therapy for NSCLC.