Venous thromboembolism (VTE) is a leading cause of death and disability worldwide. Each year, more than 10 million cases of VTE are diagnosed; studies suggest there are as many as 900,000 cases per year in the United States. The condition is estimated to cost the U.S. health care system between $7 billion and $10 billion annually. In February 2016, the American College of Chest Physicians released the 10th edition of the Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. After providing an overview of VTE pathophysiology, risk factors, signs, symptoms, and key clinical assessments, this article details recommendations from the new guideline, which incorporates the most up-to-date treatment options for patients with VTE. The authors highlight key changes from the 2012 guideline, particularly those related to nursing practice, patient education, care coordination, patient adherence, medication costs, follow-up appointments, and diagnostic testing.