The application of effective hemodialysis in humans was delayed until the development of cellulose-based membranes in 1940s, and the advent of heparin as the primary means of anticoagulation. Unfractionated heparin is still the most commonly used agent for anticoagulation, but its potentially serious complications, such as hemorrhage and heparin-induced thrombocytopenia type II, led the scientific community to consider other options to counteract coagulation. ''Low heparin dialysis'', ''heparin-free dialysis'', regional heparinization, low molecular weight heparins, citrate, prostacyclin, nafamostat, low molecular weight heparanoid and direct thrombin inhibitors are among these methods and have different safety, efficacy and cost. In general, hemodialysis patients with active hemorrhage or at high risk for bleeding complications are best treated with heparin-free hemodialysis. Low molecular weight heparanoid and direct thrombin inhibitors (recombinant hirudin or argatroban) may be useful for anticoagulation of the extracorporeal circuit in the rare patients with confirmed heparin-induced thrombocytopenia type II, who cannot be dialyzed with heparin.