An increasing knowledge of cell signal transduction pathways has led to a better understanding of multi-step bronchial carcinogenesis. This new data has been used to design new drugs targeting specific proteins involved in epithelial cell transformation. New biotherapies are a major part of the evolving strategies to fight lung cancer and actually represent a true revolution for subsets of patients. Future treatments in lung cancer patients will be tailored on the basis of routine molecular analysis of surgical and bronchoscopic biopsy specimens. Tyrosine-kinase EGFR inhibitors and VEGF inhibitors are the first molecules in this new class of therapies for lung cancer. Their mechanism of action and the resistance mechanisms that occur with these new drugs continue to be analysed, and this knowledge will help to improve the targeting of therapeutic regimes. In the same way, a better knowledge of the molecular resistance mechanisms to classical chemotherapy agents (platinum compounds, anti-metabolite agents or tubulin-interacting agents) will lead to a tailored use of these drugs, based again on the molecular characteristics of tumor specimens. The surprisingly long survivals observed among subsets of 'molecular-selected' patients, treated with frontline EGFR tyrosine-kinase inhibitors (TKIs) in still limited prospective clinical trials, could herald significant improvement in the global efficacy of lung cancer therapeutics.