Heart failure is a major public health concern for which treatment options have continued to evolve. While specific therapies such as beta blockers and angiotensin converting enzyme inhibitors have been shown to decrease hospitalizations and improve survival, the benefits of anticoagulation are less clear. Clinical guidelines detailing the appropriate use of anticoagulation for the management of atrial fibrillation and embolic stroke exist, but similar recommendations for their use in isolated cardiac dysfunction are lacking. Epidemiologic studies have documented increased risk of thrombus formation and stroke occurrence in patients with cardiomyopathy that is inversely related to ejection fraction. However, it remains at the clinician's discretion to determine at what degree of left ventricular dysfunction the potential benefits of stroke reduction outweigh the risks of undesirable bleeding with anticoagulation. This paper summarizes the pathophysiology of thrombus formation in heart failure patients; reviews previous studies and current recommendations for anticoagulation; provides a clinical rationale for anticoagulation when conclusive data are lacking; and discusses ongoing clinical trials designed to clarify these issues.