Lung malignancy is a leading cause of cancer related morbidity and mortality worldwide. The majority (85%) of cases are histologically proven non-small cell lung carcinomas (NSCLC). More than 55% of lung carcinomas harbor at least one genetic alteration, most of them being histologic subtype specific. This review summarizes the progress in personalized care of lung cancer by reviewing the literature on EGFR, ALK and KRAS molecular alterations, currently used in clinical practice, to direct the decision making process for lung cancer therapy. In addition, we will discuss some recently characterized molecular alterations whose targeting is being tested in clinical trials and holds promise for future therapeutic targeting. The role of minimally invasive procedures in lung cancer diagnosis and staging is also discussed as these techniques now play a central role in lung cancer management by providing the bulk of material for modern molecular diagnostics.