Erlotinib HCI (Tarceva; Genentech, Inc, South San Francisco, CA) is an orally available, quinazoline-based agent that competes with adenosine triphosphate for binding with the intracellular catalytic domain of epidermal growth factor receptor (HER1/EGFR) tyrosine kinase, inhibiting phosphorylation. This action blocks downstream signal transduction and inhibits the tumorigenic effects associated with ligand-dependent and ligand-independent HER1/EGFR activation. In preclinical studies, erlotinib has substantial antitumor activity against various human tumor xenografts alone and in combination with chemotherapeutic drugs. Phase I data showed that erlotinib was well tolerated, with encouraging antitumor activity in patients with various types of solid tumors. Furthermore, phase II monotherapy trials in patients with advanced non-small cell lung cancer, ovarian cancer, and head and neck squamous cell cancer, respectively, show favorable activity compared with single-agent chemotherapy in similar patient populations. Phase III trials with erlotinib in non-small cell lung cancer and pancreatic cancer are in progress, as are a range of studies in various indications designed to optimize the use of erlotinib alone and in combination with chemotherapy, radiotherapy, and other targeted agents.