Critically ill patients in the medical–surgical intensive care unit are at high risk for deep venous thrombosis and pulmonary embolism, which comprise venous thromboembolism. Herein, we describe the prevalence, incidence, risk factors, clinical consequences, prophylaxis against venous thromboembolism in critically ill patients, and compliance with thromboprophylaxis. We focus primarily on medical–surgical intensive care unit patients, who represent the largest subgroup of critically ill patients. Despite the large and growing number of critically ill patients in our aging society, their high risk for venous thromboembolism, and the morbidity and mortality associated with this complication of critical illness, relatively few rigorous studies are available. Large, well-designed, randomized trials of thromboprophylaxis, powered to detect differences in patient-important outcomes, are required to advance our understanding and care of these vulnerable patients. Furthermore, because thromboprophylaxis is a common error of omission in hospitalized patients, redoubled efforts are needed to ensure that it is used in practice.