Several research questions are open in the field of vascular access for hemodialysis. The present paper reviews both prognostic issues, such as the identification of factors for patient stratification before access insertion, and intervention questions, such as comparison of the advantages and disadvantages of different surgical solutions, the effects of different medications on vascular pathology, the different cannulation practices to prevent vessel wall lesions and technologies for early diagnosis of access dysfunction. Given that the quality of the available literature in nephrology is often suboptimal, nephrologists need to pay special attention to methodology issues before embarking on expensive multicenter studies.