Renal cell carcinoma (RCC) represents five percent of adult epithelial cancers and clear cell RCC is the most frequent histological subtype. Improved understanding of the molecular pathways implicated in the pathogenesis of RCC has led to the development of specific targeted therapies to treat the disease. Five new medications have been shown to increase progression-free survival (PFS) in patients with metastatic clear cell RCC: bevacizumab, sorafenib, sunitinib, everolimus, and temsirolimus. Bevacizumab (+ interferon-alpha), sunitinib, and temsirolimus (in poor-risk groups) have proven to be effective as first-line palliative treatments. Sorafenib has demonstrated benefits in patients that have failed prior therapy, as has everolimus after failure of sorafenib and/or sunitinib. This paper provides a comprehensive review of the new targeted therapies currently available in clinical practice to treat patients with metastatic unresectable renal cell carcinoma. The relevant patents are discussed.