Plasma fibrinogen is one of the main determinants of blood viscosity and is known to play an important role in the pathogenesis of venous and arterial thromboembolism. The pharmacological intervention on these factors can be achieved by lowering fibrinogen. Plasma fibrinogen concentrations can be lowered by fast-acting and slow-acting drugs. Among fast-acting drugs, fibrinolytic agents (such as streptokinase, urokinase, brinase and plasmin) act by cleaving FGN directly or indirectly through the formation of the proteolytic enzyme plasmin. Defibrinogenating agents (ancrod and batroxobin) are thrombin-like enzymes which induce the in vivo formation of fibrin microclots characterized by a peculiar physicochemical structure rendering them more easily cleared by the reticuloendothelial system. There is a clear-cut evidence for the clinical efficacy of fast-acting FGN-lowering drugs in the prevention and treatment of a number of clinical conditions associated with thromboembolic manifestations. However, it is not well established to which extent the effectiveness is due to their action on blood viscosity rather than to their fibrinolytic and anticoagulant properties. Slow-acting drugs (such as anabolic steroids, clofibrate, ticlopidine and pentoxifylline) decrease plasma FGN less rapidly and to a smaller extent than fast-acting drugs. Unlike these, they can be employed in long-term treatments. Clinical trials have clearly shown their clinical efficacy in a number of conditions associated with an altered microcirculation (Raynaud's syndrome, liposclerosis and postphlebitic syndrome). Their effect on blood viscosity is likely to be an important determinant of the clinical efficacy of these drugs.