Refractory or recurring leg ulcers typically signify the presence of impaired venous or arterial microcirculation (or both). A current hypothesis suggests that local oxygen and nutrient deficits occur because capillary lumens narrow and become permeable to fibrinogen and proteins by activated white blood cells and inadequate fibrinolysis. As a result, the deposition of a relatively impermeable perivascular fibrin sheath occurs, preventing adequate delivery of oxygen and nutrients. Therapy should therefore aim at reversing these deficits and improving wound healing. Pentoxifylline (Trental), used in combination with local wound care and appropriate antibiotic therapy, has been successful in significantly improving the healing of refractory leg ulcers. Pentoxifylline can reverse the abnormal function of white and red blood cells and platelets, as well as reduce blood viscosity and vascular permeability. The mechanisms of action of pentoxifylline are described in light of current hypotheses pertaining to leg ulcer development. Also discussed are nine cases in which pentoxifylline, when added to previously unsuccessful local wound care, either improved or healed the refractory ulcers.