Venous thromboembolism is a major cause of morbidity and mortality worldwide and most often affects hospitalized postoperative surgical and medical patients. Venous thromboembolism prophylaxis undoubtedly improves the care of these patients, as demonstrated by the current literature and guidelines. Failure to prescribe prophylaxis when indicated, however, remains a vital health care concern. The American College of Chest Physicians (ACCP) published their most recent guidelines regarding venous thromboembolism prophylaxis in 2008. In this review, we aim to summarize the most recent ACCP prophylaxis guidelines with practical application and interpretation for the practicing physician. Here we present the most practical information from these guidelines and summarize essential recommendations in key tables. We will briefly review the grading system used in the guidelines for the level of evidence and the strength of the recommendation. We will then discuss the recommendations for prophylaxis in the various patient populations described in these guidelines including general and orthopedic surgery, gynecologic surgery, urologic surgery, thoracic surgery, neurosurgery, trauma, medical conditions, cancer patients, and critical care. In addition, we will discuss recent clinical trials regarding novel anticoagulants for venous thromboembolism prophylaxis and share some conclusions.