Patients with advanced lung cancer and poor performance status (PS) have been underrepresented in clinical trials. As a consequence, the management of these patients in clinical practice is empirical and inconsistent. Recent data in advanced non-small-cell lung cancer (NSCLC) indicate that patients with a PS of 2 tend to benefit from first-line chemotherapy with respect to symptom improvement and perhaps overall survival. Whether single-agent therapy or combination chemotherapy is preferable remains debatable. In previously treated patients with NSCLC, gefitinib produced a substantial rate of clinical benefit, and erlotinib led to an improvement in survival compared with placebo in studies that included a significant percentage of patients with poor PS. In patients with recurrent small-cell lung cancer, who frequently present with a compromised PS, the use of topotecan as a single agent led to an improvement in PS in approximately one third of these patients without excessive toxicities. Patients with advanced lung cancer and a PS of 2 have been the focus of intense clinical investigation in recent years. When more specific data for this special population become available, it will hopefully lead to more consistent management and improved outcomes.