The ground-breaking article by Brescia and Cimino in 1966 (1) revolutionized the creation of the vascular access, and the Cimino fistula was soon used in almost all dialysis patients. Unfortunately, subsequent wide-spread use of PTFE grafts instead of AV fistulae occurred because of the ease of the surgical technique, the immediate availability of the graft for puncture, the need of high blood flow for high-efficiency, short-duration hemodialysis sessions, and because of financial disincentives against the AV fistula. PTFE grafts currently account for 80% of primary vascular accesses created in the United States (2,3), but they are less frequently used in other countries. It has been increasingly recognized that outcomes of PTFE grafts are poorer. In the DOQI guidelines (4), this has led to the recommendation that AV fistulae should be the first option; however, this advice has not been followed uniformly. One impediment may be the astonishingly high rate of primary failures of AV fistulae, up to 50% in some centers (4). The DOPPS study (Figure 1) documented substantial differences between survival of PTFE grafts and AV fistulae and differences of survival of AV fistulae between the United States and other countries (3). On the basis of our experience, we are of the opinion that primary failure rates can be substantially improved by attention to small but important details of surgical technique. The DOQI guidelines state that AV fistulae are feasible only in 50% of the patients, but we (5) and others (6) found that construction of native AV fistulae is feasible in up to 90%.It is the purpose of this article (a) to provide some insights into the fascinating cellular biology and pathophysiology underlying the vascular adaptation to the creation of an AV fistula and (b) to describe some small, often neglected, but important technical details that determine the success of the procedure. It is the intention to improve results and to influence patterns of practice.