Deep vein thrombosis (DVT) affects an estimated 500,000 to 2 million people in the United States per year. Approximately 250,000 hospital admissions occur annually, with an estimated length of stay between 24 hours and 7 days. Complications include recurrent nonfatal thromboemboli, postthrombotic syndrome, and fatal pulmonary embolism. The standard of care for these patients is constant infusion of unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). Thus the goals of therapy are to prevent thrombus propagation, thrombus embolization, and early and late recurrence. Proper anticoagulation is the first critical step in effective treatment of DVT; however, secondary prevention is equally important. This article reviews the treatment algorithms for UFH, dosing of LMWH, and management strategies for secondary prevention as represented in the current literature. The goals for dosing UFH are either to use a weight-based nomogram or standard dosing schedule with an appropriate infusion rate to achieve a therapeutic activated partial thromboplastin time within 24 hours. Failure to do so may result in a 23.3% frequency of VTE, compared with a frequency of 4% to 6% with therapeutic thresholds within 24 hours (P = 0.02) when treated with a standard dosing schedule of UFH. A weight-based UFH nomogram resulted in a significantly faster titration to therapeutic levels, 97% by weight based versus 77% by standard dosing (P = 0.002). Over the past 4 years, a number of published meta-analyses of randomized controlled trials support that LMWHs are either better than or equal to UFH and cause less major bleeding and a lower incidence of thrombocytopenia. Duration of therapy and alternatives to warfarin are the issues associated with secondary prevention. Presently patients continue warfarin therapy for 3 to 6 months with a target international normalized ratio between 2.0 and 3.0. The American College of Chest Physicians (ACCP) Guidelines recommend long-term treatment with LMWH for at ≥3 to 6 months for most patients with PE and concurrent cancer. In conclusion, effective VTE therapy consists of 2 phases: the initial achievement of therapeutic anticoagulation and the prevention of recurrent thromboembolic events. Both may be achieved with UFH or LMWHs. Patients who present with recurrent thromboembolic events with idiopathic VTE should be treated with a medication regime of warfarin administered for 6 to 12 months, although clinical trials suggest that treatment for up to 2 years may be clinically beneficial. Additionally, low-intensity warfarin administration is valuable in patients at high risk for bleeding. LMWH presents an increased profile of safety and efficacy in individuals with an underlying malignancy.