Irinotecan has recently been found to be one of the most active agents in the treatment of small-cell lung cancer (SCLC). Japanese investigators have led the way in the early investigation of irinotecan, and multiple studies are now ongoing in the United States. In a phase II trial conducted by the West Japan Thoracic Oncology Group, irinotecan was associated with a median survival of 13 months in patients with extensive-stage disease. Subsequently, the Japanese Clinical Oncology Group completed a phase III trial comparing irinotecan plus cisplatin to cisplatin and etoposide. In this study, median, 1-year, and 2-year survival rates were superior with irinotecan and cisplatin. Two confirmatory phase III trials are in progress in the United States. Based on these early data, it is likely that irinotecan and a platinum agent will prove to be at least as effective as any other treatment for patients with extensive-stage SCLC. Investigators have embarked on combining irinotecan with carboplatin in anticipation that this will be a preferable treatment. Phase I/II trials are complete and the doses and schedules have been recommended. As a result, we are currently exploring irinotecan and carboplatin in phase II trials in both extensive- and limited-stage settings. In addition, several of the newer biologic targeted agents are being tested in SCLC in combination with newer chemotherapy regimens. The results from these trials are eagerly awaited.