The native arteriovenous fistula (AVF) is considered the best access for hemodialysis due to its longer survival and lower complication rates as compared with other forms of vascular access. However, broad practice variation exists in the use of AVF among different countries and even within the same country among different regions and centers. Several barriers to AVF placement have been identified in the last decade that might explain its suboptimal use among both prevalent and incident patients. The present review summarizes and discusses recent findings from epidemiological studies on practice patterns and risk factors for AVF failure. Special emphasis is devoted to drawbacks and payoffs consequent upon the choice of the AVF as access for dialysis. In fact the AVF requires major investments in the short run but far less assistance and rework thereafter. Primary AVF failure, due to early failure or lack of maturation, is currently considered a key area of investigation to improve vascular access outcomes. The main challenge for the nephrologist today is to minimize the risk of primary failure while attempting to provide most patients with a native AVF. Improving vascular access outcomes is clearly a complex and difficult task. Recent experience from the United States suggests that multidisciplinary management is the most appropriate approach to deal with all the multifaceted aspects of end-stage renal disease care and to increase the likelihood of success.