Lung cancer has seen a paradigm shift in disease treatment over the past few years, with major changes in the therapeutic drugs now available as well as in the overall management approach. For targeted and immunotherapeutic approaches, understanding the biology of acquired resistance is a key strategy that has yielded productive advances in the subsequent treatment. Future advances also include incorporating biomarker data obtained from solid and liquid biopsies, as well as combination of immunotherapy with radiotherapy and in special populations such patients with CNS involvement.