Renal cell carcinoma is the most common form of kidney cancer worldwide, and is associated with poor survival. Approximately a third of patients diagnosed with renal cell carcinoma present with metastatic disease and a further third experience recurrence following treatment for localized disease. Until recently, the cytokines interferon-alpha and interleukin-2 were the only effective treatments available for metastatic renal cell carcinoma and were associated with a modest increase in survival in a limited subset of patients. The prognosis for metastatic renal cell carcinoma has dramatically improved with the development of novel targeted agents including the oral tyrosine kinase inhibitors, sunitinib and sorafenib. However, renal cell carcinoma and the therapies used to treat patients with renal cell carcinoma are associated with a range of symptoms and treatment-related adverse events which contribute to the burden of disease. Common adverse events associated with targeted agents include fatigue, gastrointestinal and skin-associated toxicities. These adverse events, while mostly mild and manageable, affect the patients' health-related quality of life. As this review of the available quality of life data shows, assessment of the impact of the disease and its treatment on health-related quality of life may influence the choice of treatment and highlights the importance of incorporating patient-reported outcomes in clinical trials.