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With recent improvements in the prognosis for patients with metastatic renal cell carcinoma (mRCC), focus is now shifting towards maximising clinical benefit from targeted therapies. Factors other than efficacy data are increasingly being considered when selecting a treatment strategy, with a view towards optimising clinical outcomes.This review examines the development and efficacy of targeted agents for the management of mRCC and discusses the potential factors, including resistance mechanisms, sequential therapy, prognostic and predictive markers of response, and adverse event management, that may contribute to successful individually tallored treatment of patients with this disease.Targeted agents have substantially improved outcomes for patients with metastatic renal cell carcinoma (mRCC).Treatment focus is now shifting towards achieving a continuum of care such that long-term benefit and extended survival may be achieved through the optimal use of targeted agents.To achieve this goal, a number of factors which impact on treatment selection and outcomes need to be considered when treating patients with mRCC, such as the optimal sequence of targeted therapies (and the related issue of resistance mechanisms).Recent advances are also likely to impact on the future treatment of mRCC. Examples include the identification of predictive biomarkers as well as a consideration of patient risk profiles or the safety profile of the selected targeted agent. In addition, attention is focusing on re-defining the role of surgery for the treatment of RCC in the context of targeted therapies.This review examines the recent and future advances that offer the potential for personalizing treatment by selecting the most appropriate treatment for each patient with a view towards optimizing clinical outcomes.