Findings from observational studies have established that the arteriovenous fistula (AVF) is the preferred form of vascular access for chronic hemodialysis. Unfortunately, in a subset of patients with end-stage renal disease, an AVF cannot be placed or fails to mature. In these patients an alternate form of vascular access, either an arteriovenous graft (AVG) or central venous catheter (CVC) must be selected. In this review we discuss the findings and limitations of studies examining the effect of access type (AVG or CVC) on clinical endpoints including mortality, quality of life, occurrence of infections, as well as the impact of the different access types on resource requirements. Specifically, we examine whether findings from previous studies are valid and applicable to patients for whom an AVF is not possible, and outline the need for future randomized clinical trials addressing this question.