Small cell lung cancer (SCLC) accounts for 25% of all cases of lung cancer diagnosed in the United States. The sensitivity of SCLC to chemotherapy offers good prospects for prolonged remission and long-term survival. Over the last decade, however, the overall response rate and median survival in SCLC patients have remained essentially unchanged. Single-agent intravenous (IV) etoposide has proven to be among the most active drugs for the treatment of SCLC. Oral or oral plus intravenous etoposide has been used in many combination chemotherapies. Studies demonstrating the schedule dependency of etoposide suggest that optimum results would be achieved if the total were administered over a minimum of 5 days. Given in such a schedule, oral etoposide has been shown to be effective in unfit or elderly (> 70 years of age) patients with SCLC, who represent 25% to 30% of the total SCLC population. Prolonged etoposide administration has achieved efficacy comparable with that attained in 5-day schedules, but with notable toxicity. Moreover, the value of dose intensity in single-agent and combination regimens employing etoposide has recently been questioned. New therapeutic strategies are clearly needed to increase the response rate, to prolong survival, and to improve quality of life in SCLC patients.