Over 25,000 people are diagnosed with small-cell lung cancer (SCLC) in the United States annually. SCLC is a highly aggressive tumor with a propensity for early metastases and a high case-fatality rate. Systemic treatment with etoposide plus a platinum agent is recommended for all stages of this disease and has been a standard first-line therapy for SCLC since the 1980s. Three recently presented randomized clinical trials failed to show superiority of newer regimens over etoposide and cisplatin. Patients with limited-stage (LS) disease benefit from the addition of radiotherapy to systemic chemotherapy, a combination that affords high complete response rates and potential cures. Incremental improvements in radiotherapy delivery over the past decade include the use of accelerated hyperfractionated thoracic radiotherapy for LS disease. Prophylactic cranial irradiation, previously recommended for patients with LS disease, has recently been shown to benefit those with extensive-stage (ES) disease as well. Surgery, largely abandoned in the 1970s, is being reevaluated as primary local therapy in patients with very early-stage SCLC. Topotecan remains the only US Food and Drug Administration-approved therapy for recurrent disease. Amrubicin has demonstrated single-agent activity in multiple phase II trials in both chemotherapy-sensitive and -refractory relapse. The past 2 decades have been marked by an improved understanding of SCLC biology, and these discoveries are reflected in the number and diversity of novel therapies entering early-phase testing in this disease.