Major advances in the treatment of metastatic non–small cell lung cancer have led to significant incremental improvements in patient outcomes. Platinum-based combination therapy remains the cornerstone of first-line therapy. The addition of biologic agents, such as bevacizumab or necitumumab, in selected populations has shown benefit over chemotherapy alone. The advent of maintenance therapy has also improved overall survival outcomes in selected populations of patients. Ongoing studies will further refine optimal treatment in the first-line setting and further advance first-line treatment options.