Background Renal cell carcinoma accounts for 3% of all solid tumors and currently causes about 3,500 deaths/year in the UK. Once an orphan disease, it has undergone an impressive change in its natural history with an improvement in overall survival, thanks to the development of new target agents. Introduction In its management, renal cell carcinoma has been treated with both surgical and medical approaches. Nowadays, many more drugs are available, especially in the metastatic setting, so that we should reconsider the peculiar role of surgery and its interaction with target agents. Conclusions Cytoreductive nephrectomy still plays a major role in the management of the disease, though no really solid data have been still obtained. Adjuvant and neoadjuvant settings, instead, are still under evaluation, especially new adjuvant therapies involving the numerous target agents we have. Finally, metastasectomy has a controversial role, with some evidence of more efficacy than the medical treatment, though it shows too many biases to be considered certain. The picture that comes out suggests a complex frame, in which we have great power to act, but in which we need to better comprehend the interactions that could be created between surgery and medical therapies, to achieve an optimal multimodal treatment for renal cell carcinoma.