The limitations of the Response Evaluation Criteria in Solid Tumors (RECIST) for the assessment of molecularly targeted agents have been increasingly recognized with the advance of new therapies. The current study and others focusing on vascular endothelial growth factor-pathway inhibitors in advanced renal cell carcinoma highlight that tumor shrinkage below the RECIST threshold can be associated with significant clinical benefit, and flexibility in size change categorization should be considered in future modification of the criteria.