Primary aim of nephrectomy was palliation of intractable hematuria, pain and paraneoplastic syndromes in patients with renal cell carcinoma (RCC). Cytoreductive nephrectomy has a well-established role in the treatment of appropriately selected patients with metastatic RCC prior to cytokine therapy. Recent use of novel molecular targeted agents in the management of metastatic RCC has challenged the current dogma of treatment with regards to the necessity, patient selection for and timing of cytoreductive nephrectomy. The evidence that we have suggests that cytoreductive nephrectomy still plays an integral part in the multimodal paradigm of the treatment of metastatic RCC. This review highlights the role of cytoreductive nephrectomy and discusses controversial issues for cytoreductive nephrectomy in the treatment of metastatic RCC in the era of targeted therapy.