Targeted therapy has survival benefit for patients with advanced renal cell carcinoma. However, intolerability often causes discontinuation of treatment. Therefore management of adverse events and maintenance of treatment duration as long as possible are absolutely essential for patient care. Hypertension is a common adverse event of vascular endothelial growth factor receptor (VEGFR) inhibitors. General symptoms such as fatigue or asthenia and gastrointestinal disorders including diarrhea, nausea, and anorexia are also frequently produced by VEGFR inhibitors as well as other targeted agents under development. Development of a new drug which does not cause any severe adverse event may be an ultimate strategy against adverse events of current targeted agents. Here we review the adverse-event profiles of targeted therapies being developed, including axitinib, tivozanib, dovitinib, AS1411, vorinostat, AMG386, BMS-936558, carfilzomib, IMA901, and AGS-003, for renal cell carcinoma.