In 1980, unfractionated heparin (UFH) was the established agent for the prophylaxis of venous thromboembolic (VTE) disease in patients undergoing general surgery. VTE prophylaxis was the first indication in which low-molecular-weight heparins (LMWHs) were tested. Approximately 40 trials have demonstrated that LMWHs are at least as effective and safe as UFH. LMWHs exhibit a number of advantages over UFH, including ease of administration, convenient once-daily dosing, and facilitation of outpatient management. The ideal time of administration and the dose of the initial one or two injections of LMWH remain unresolved issues. LMWHs are used with increasing frequency in the treatment of acute deep vein thrombosis (DVT), having been studied in comparison to UFH in 16 major clinical trials. LMWHs are at least as effective as UFH in the prevention of VTE, but higher doses than those used for prophylaxis are required. There is still an ongoing debate about whether the daily dose should be administered in one or two subcutaneous injections. In some recent studies, symptomatic new DVTs or pulmonary emboli (PE) were the primary end points, which had to be verified by objective methods, but such end points may be not be sensitive enough to detect major differences in the efficacy of different LMWHs.