Anti-angiogenetic agents are currently considered standard therapy for metastatic renal cell carcinoma (RCC) for the majority of the patients. In contrast to immuno- or chemotherapy, the inhibition of specific signaling pathways has been considered essentially non-toxic. The advance of these tyrosine kinase inhibitors into clinical practice has led to a more detailed understanding of their targets in both, the tumor and the patient. At the advent of targeted therapies, oncologists are in the process of developing surveillance strategies tailored for specific side effects of individual classes of agents to the individual needs of patients. In the current article, the significance of adverse events and their management in RCC patients is reviewed in order to guide the clinical oncologist through patient surveillance and treatment of adverse events.