Nephrotic-range proteinuria, which denotes structural damage to the glomerular filtration barrier, occurs in 1–2% of bevacizumab-treated patients. The glomerular injury and subsequent proteinuria is probably due to a direct targeting of vascular endothelial growth factor (VEGF). We report a case series of six patients who developed a syndrome characterized by proteinuria and hypertension after starting therapy with bevacizumab and who experienced prolonged progression-free survival. Given that altered glomerular permeability appears to be a direct consequence of VEGF inhibition, we hypothesize that proteinuria may indeed correlate with drug efficacy. Optimizing safe and effective drug dosing is critical to achieve the best therapeutic impact due to limited treatment options for many life-threatening advanced cancers. Clinicians should be aware that the development of proteinuria might serve as a surrogate marker of bevacizumab antitumor efficacy and determine the appropriate criteria for withholding this effective anticancer therapy.