Lung cancer is one of the most frequent causes of death from cancer. Non-small cell lung cancer represents approximately 80% of the total pulmonary malignancies. Unfortunately, most non-small cell lung cancer patients present advanced disease at diagnosis and a very poor prognosis. Despite advances in our understanding of the molecular and genetic basis of non-small cell lung cancer, and improvement in therapy with surgery, conventional chemotherapy, and radiation, 5-year survival for patients with this diagnosis remains poor and the disease remains a clinical challenge. However, strategies of molecular based therapies are in development and it is hoped that these new approaches will continue to improve survival for patients with advanced lung cancer. Any categorization of these drugs is hard, with overlap in several features. The main investigated agents are epidermal growth factor receptor (EGFR) family inhibitors, angiogenesis inhibitors and antivascular drugs, signal transduction inhibitors, apoptosis inducers, eicosanoid pathway inhibitors and immunotherapeutic drugs. To date, few of these new drugs can offer trust of a substantial influence on the natural history of non-small cell lung cancer, and disappointing results are more commonly reported than encouraging ones. Nevertheless, tailored treatment for non-small cell lung cancer patients may represent a further chance of tumor control and symptom palliation. This review presents an overview of molecular targeted therapy in non-small cell lung cancer.