In this special issue of Translational Lung Cancer Research (TLCR), we touch on new developments of pharmacotherapeutic strategies for advanced NSCLC, specifically focusing on the present and future evolution of systemic treatments for BMs. Included manuscripts cover the following areas: TKIs (with or without RT), chemotherapy, antiangiogenic treatment and immunotherapy. In addition, one paper focuses on less invasive radiation techniques such as hippocampal sparing WBRT. Finally, another review reports on whether criteria exist for defining the response of BMs to treatment, with the final intent of providing comparative measurement of effectiveness across multiple trials with different drugs. We really thank the authors for their vital contribution to this special issue, and hope that all readers involved in the treatment of NSCLC will find this issue of valuable interest and keep it as valid reference for their work.