Venous thromboembolism (VTE) is one of the most frequent and serious vascular diseases. Although the major risk factors of VTE are well recognized, the pathology often develops in subjects without any obvious precipitating factor. Recent evidence suggests a link between arterial and venous thrombosis, particularly in patients with idiopathic venous thrombosis. Therefore, similar or identical risk factors may play a role in the development of both diseases. A positive association between classical risk factors of atherosclerosis, including dyslipidemia, and VTE has been reported. Recent studies demonstrated an association between hypercholesterolemia and objectively verified VTE. Circulating lipids have been shown to have both prothrombotic- and endothelium-deteriorating properties. Studies suggested a greater generation of thrombin, endothelial dysfunction, and higher platelet activity in hyperlipidemic blood. By impeding these mechanisms, statins may protect against VTE. Observational, controlled studies and two meta-analyses showed that statins significantly reduced VTE risk, most likely in a process independent from cholesterol lowering, through mechanisms related to the pleiotropic effects of these drugs. Currently, it is unknown whether VTE prevention is a class-effect of statins, or if statins differ in their antithrombotic efficacy, and it is also unknown if statin benefit is dose-dependent. However, there are also opposite findings about the efficacy of statins in prevention of VTE. Therefore, the use of statins for prophylaxis of VTE cannot be generally recommended at this stage. Further studies are needed to identify those patients who could eventually benefit maximally from treatment with statins for prevention of VTE.