Malignant pleural effusion (MPE) causes significant morbidity in cancer patients. Management is often challenging because of the recurrent nature of MPE and the inconsistent response rates of various treatments. In patients whose underlying malignancy is unresponsive to systemic chemotherapy or radiation, MPE is usually managed by tube thoracostomy with subsequent sclerotherapy. Selection of a sclerosing agent should be based on several factors, including efficacy, toxicity, cost, and convenience. Of the numerous agents available for managing MPE, doxycycline, bleomycin, and talc have emerged as the most promising. Even these agents have disadvantages, such as the high cost of bleomycin and the possible need for multiple dosing of doxycycline. Talc is clearly the most controversial of the three. Although its efficacy is well documented, its role remains unclear because of its unattractive side effect profile and inconvenient preparation and administration. Results of controlled comparative trials are needed to identify the optimal sclerosing agent.