The advent of novel targeted agents for metastatic renal cell carcinoma (RCC) has offered clinical benefits over traditional immunotherapy (e.g., interleukin-2 and interferon-alpha) in both efficacy and safety profiles. The major classes of these targeted therapies for metastatic RCC include the tyrosine-kinase inhibitors, monoclonal antibody against vascular endothelial growth factor, and inhibitors of the mammalian target of rapamycin. Most recently, the success of immune checkpoint inhibitors notably antibodies directed against programmed death-1 and its ligand-has also been demonstrated in RCC. With such progress in therapy, early detection, and subsequent management of treatment-related adverse events allow for patients to remain on active therapy for as long as possible and also enhance the probability of patients tolerating subsequent second line options. However, despite such impressive gains in efficacy with these new agents, therapeutic progress are primarily palliative in nature-hence, the critical importance of minimizing discomfort and potential harm in this patient population cannot be understated. (C) 2015 Elsevier Inc. All rights reserved.