For 50 years, the key to successfully preventing venous thrombosis (VT) or pulmonary embolism (PE) among high-risk patients has been the judicious use of anticoagulants: first through full doses of oral anticoagulants and more recently through low-dose heparin prophylaxis. Low-dose heparin has become the standard of comparison for other preventive methods, since it is relatively safe and simple, its ability to prevent approximately 65% of the subclinical VT found by leg scanning after elective general surgery is well known, and recent meta-analysis of the many pertinent published clinical trials (large and small) strongly suggests a much greater benefit: a 65% reduction in the risk of postoperative death from major PE. In addition, there are trials that have also found low-dose heparin to be effective in general medical patients, although its value in this clinical setting is much less well documented. Although several effective approaches other than low-dose heparin are available, many of these tend to be either more cumbersome (intermittent external leg compression) or probably less powerful (graded pressure elastic stockings). There are situations where low-dose heparin prophylaxis fails, most obviously after orthopaedic surgery where the use of more complex regimens, including adjusted-dose heparin treatment and various schedules of warfarin prophylaxis, becomes appropriate. Recent progress has come from the intensive clinical exploration of various low molecular weight heparin fractions or fragments which appear to be effective after once daily administration to general surgical patients and show great promise of effectiveness and safety after hip surgery. The level of warfarin effect needed for VT prophylaxis has also been reinvestigated, with trials suggesting a need for less warfarin and a lower prothrombin time effect than was previously thought to be appropriate. Given that any attempts to minimize mortality from PE in hospital patients must rely on the widespread and systematic use of simple, safe, and cost-effective preventive methods, it is hoped that these advances will help move anticoagulant prophylaxis further out of the realm of clinical research and into that of common clinical practice.