Advances in targeted therapies for the treatment of non-small cell lung cancer (NSCLC) has delivered expanded treatment options against targetable alterations including EGFR, ALK, ROS1, KRAS, MET, BRAF, RET, NTRK, and HER2. Previously limited to the treatment of advanced disease, recent and ongoing trials have demonstrated benefit in early stage disease with new and expanded indications likely forthcoming. The ever increasing number of targets and expanding indications mean that a greater proportion of NSCLC patients will receive targeted therapies. Appropriate toxicity management is important to maintain quality of life, support adherence, and allow continuation of these highly effective treatments. Common and serious toxicities include skin, gastrointestinal, and hepatic toxicities, fatigue, and oedema. Class and agent specific toxicities include vision disorders, hypertension, dyslipidaemia, pneumonitis and others. Interventions for symptom control with or without dose reduction or dose delay can allow continuation on therapy in many cases. Discontinuation due to treatment related toxicities is sometimes necessary, however treatment related deaths are rare. An overview of toxicity profiles and management and supportive care strategies for Australian approved therapies, as well internationally approved and emerging therapies on the horizon for entry into routine care in Australia, will be provided. Approaches for toxicity prediction and identification of at-risk patients, and strategies to limit toxicities including the potential role of therapeutic drug monitoring, will be presented.