Antiangiogenic therapies interacting with tumor-specific pathways have been established for targeted therapy of renal cell carcinoma (RCC). However, evaluation of tumor response based on morphologic tumor diameter measurements has limitations, as tumor shrinkage may lag behind pathophysiological response. Functional imaging techniques such as dynamic contrast-enhanced (DCE) ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI), unenhanced diffusion-weighted MRI (DW-MRI), and also metabolic imaging with positron emission tomography (PET) have the ability to assess physiological parameters and to predict and monitor therapy response. Assessment of changes in vascularity, cellularity, oxygenation, and glucose uptake with functional imaging during targeted therapy may correlate with progression-free survival and can predict tumor response or progression. In this review, we explore the potential of functional imaging techniques for assessing the effects of targeted therapy of RCC and as well review the reproducibility and limitations.