The discovery of diverse driver mutations in lung cancer has heralded a new era of personalized medicine in thoracic oncology, with targeted therapies approved for specific subgroups of patients. The increasing number of patient subgroups that may respond to targeted therapy has resulted in a greater reliance upon effective and increasingly complex diagnostics, which must be interpreted in an interactive multidisciplinary forum. This review discusses the molecular diagnostics available and under development for established and emerging targets, and how these may be integrated into current treatment algorithms. The roles of the pulmonologist, interventional radiologist, thoracic surgeon and molecular pathologist are discussed, and their interactions with the medical oncologist, and/or thoracic surgeon and radiation oncologist in making individual treatment decisions.