A series of phase II and randomised phase III trials in Asia and Europe have confirmed recently that advanced stage non-small-cell lung carcinoma patients with adenocarcinoma subtypes harbouring specific mutations when subjected to targeted therapy experience equivalent survival outcomes as those treated with chemotherapy and are spared from its side effects. The concept of chemotherapy for all is fading, and therapy optimisation has emerged as a paradigm shift in treatment. This article briefly describes cellular mechanisms involved in lung carcinogenesis which provide a molecular basis for targeted therapy. Advances in molecular biology have improved our understanding of mechanisms involved in primary or secondary drug resistance. Evolving biomarkers of prognostic and predictive importance, and the impact of translational research on outcomes are also covered. A marker is considered prognostic if it predicts the outcome, regardless of the treatment, and predictive if it predicts the outcome of a specific therapy.