The well-known association between vesicoureteral reflux and urinary tract infection is the basis for pathophysiological and therapeutic implications which have dominated the literature on the subject for the last 2 decades. We critically review the following issues: (1) does urinary tract infection cause reflux? (2) does reflux predispose to infection? (3) does reflux predispose to pyelonephritis? (4) does reflux predispose to a renal parenchymal scar? (5) does long-term urinary antibiotic prophylaxis prevent renal damage in patients with reflux? We conclude that none of the reviewed issues have been rigorously proven or validated and that the role of vesicoureteral reflux in urinary tract infections needs to be redefined through well-designed, multicenter, prospective, randomized, controlled studies using state of the art renal imaging techniques.