The development of targeted therapies has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), with new clinical trials and therapies consistently providing new information. This rapidly changing field mandates ongoing education for nursing professionals whose foremost priority is patient care. This review aims to summarize the history and current status of targeted therapies for NSCLC, focusing on two types of drugs that have had the most impact to date. The safety profiles of first- and second-generation EGFR and ALK inhibitors are described, and strategies for the management of the most commonly experienced adverse events are summarized. Information is also provided to help identify which patients might be eligible for treatment with EGFR or ALK inhibitors in addition to the implications of targeted therapies. Therapies designed to target specific molecular features of individual tumor cells are one of the most important developments in treating NSCLC. The safety profiles of targeted therapies differ greatly from chemotherapy and present unique challenges to nurses. Education of nurses and patients on implementation of effective adverse event management and improvement in patient adherence will maximize the benefits of these drugs.