OBJECTIVE: Renal cell carcinoma has an asymptomatic course and 25-30% of patients present with metastatic disease at time of diagnosis. Molecularly targeted therapies (MTTs) represent a breakthrough in treatment of mRCC, prolonging life, reducing toxicity and the negative impact of treatment on health-related quality of life (HRQOL), and offering viable therapeutic options to a broader patient population relative to immunotherapy. The objective of this study was to explore the burden of mRCC and the potential clinical, economic and humanistic value of MTTs. METHODS: PubMed, scientific meeting and online databases were searched for articles relating to the epidemiologic, humanistic and economic burden of mRCC. Thirty-five articles were selected. Epidemiology and economic statistics for mRCC were estimated from international registries and published data sources. RESULTS: Approximately 1500-8600 new mRCC cases occur annually in major European and North American countries, and Japan. Standard immunotherapy is largely ineffective (less than 10% response rates; no benefit in most patients, especially the elderly) despite a high annual cost of treatment (e.g., $15,500-$82,000 across countries). In the absence of effective treatment, mRCC is rapidly fatal with 13% or fewer patients surviving and a median survival of less than 1 year. Two-year costs of care for mRCC have been estimated at $35,735/year (US$). HRQOL of mRCC patients is comparable to congestive heart failure, diabetes and other cancer patients and may be further diminished by systemic immunotherapy. Recent studies show that MTTs produce marked improvements in response rates/survival, and tolerability without negative impact on HRQL. CONCLUSIONS: The need for MTTs for mRCC is characterized by the lack of effective treatment for the vast majority of patients, high mortality, and considerable humanistic and economic burden. Meaningful improvements in effectiveness and tolerability in this patient population suggest that MTTs offer economic and humanistic value in the treatment of mRCC.