Non-small cell lung cancer (NSCLC) is a major global health problem and represents the leading cause of cancer-related deaths worldwide. The majority of patients with NSCLC are diagnosed with advanced-stage disease, and the prognosis for such patients is poor. The currently approved cytotoxic chemotherapy is associated with substantial limitations in both efficacy and safety. The availability of agents targeted against the epidermal growth factor receptor (EGFR), as well as the antiangiogenic agent bevacizumab, have provided some clinical benefit. Nonetheless, the efficacy of these agents is also inadequate, and resistance has emerged as a clinical problem. Numerous novel targeted therapies are now in clinical development and may have potential for overcoming the limitations associated with currently available agents. In this article we review clinical data for molecular-targeted therapies in NSCLC, with emphasis on EGFR inhibitors and antiangiogenic agents.