Acetate-free biofiltration (AFB) is a hemodiafiltration technique that, technically as well as biologically speaking, has all the premises for being a perfectly biocompatible technique capable of satisfying even the demands of critical patients laden with comorbidities. Important clinical benefits to patients have been reported, such as a better correction of acid-base balance, an improved nutritional status and a better hemodynamic stability. In particular, as far as the cardiovascular instability is concerned, several studies have shown that the rationale behind a better hemodynamic stability is the overall absence of acetate usually present in the dialysis bath, which often leads to an impaired vascular tone and a reduced cardiac contractility. One of the powerful features of AFB is its adaptability to new devices and tools which can be easily and safely used. In AFB, potassium modulation in the dialysate is easily achieved. Thus, patients with elevated levels of predialysis potassium and a tendency to develop both intra- and interdialysis arrhythmias benefit most. Lastly, the possibility to associate AFB with devices like Hemocontrol (which allows for a feedback conditioning of blood volume) broadens its practical scope, not only for use with hypotension-prone patients, but also with hypertensive patients with massive increases in their interdialysis body weight. In this category of patients, avoiding the risk of dangerous hypovolemias allows for the achievement of dry body weight, thereby facilitating the control of arterial blood pressure and minimizing the clinical consequences of a chronic fluid overload.