A water soluble derivative of camptothecin, irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC), as well as non-SCLC and gastrointestinal cancers. This extended review of recently concluded and ongoing studies focuses on irinotecan in the treatment of limited (LD) and extensive (ED) SCLC specifically considering the safety of patients. Irinotecan-induced diarrhoea is pervasive, and can be severe and life-threatening especially in combination with neutropenia. It can have a significant impact on patient quality of life, negatively influencing compliance with therapy and dose-intensity. For LD SCLC, irinotecan can be administered with radiotherapy concurrently or sequentially. In a Phase III study for ED SCLC comparing etoposide and cisplatin (EP) and irinotecan and cisplatin (IP) regimens, severe myelosuppression was more frequent in the EP arm than in the IP arm, and conversely severe or life-threatening diarrhoea was more frequent in the IP arm than in the EP arm. IP resulted in significantly higher response rates and overall survival in Japan, and confirmatory Phase III studies are ongoing. Irinotecan should not be administered to patients with any degree of ongoing diarrhoea above their baseline. Irinotecan can be administered with relative safety for patients with SCLC only through careful patient monitoring, especially regarding diarrhoea and myelosuppression.