The rapid evolution of targeted therapies has had a dramatic impact on multiple domains in oncology, particularly metastatic renal cell carcinoma (RCC). Four agents antagonizing vascular endothelial growth factor-mediated signaling have been approved for the treatment of metastatic RCC, including the monoclonal antibody bevacizumab and the small molecular inhibitors sunitinib, sorafenib, and pazopanib. Pazopanib was approved in 2009 for this disease on the basis of a phase III clinical trial demonstrating a superior progression-free survival compared to placebo in 435 patients with either treatment-naive or cytokine-refractory disease. The trial offered insight related to the toxicity profile associated with this agent. The most common clinical adverse events are diarrhea, hypertension, nausea, anorexia, and vomiting. With respect to laboratory adverse events, hepatotoxicity represents a specific concern with pazopanib. Oncology nurses play a critical role in counseling patients regarding the toxicity profile and management of adverse events in pazopanib treatment.