Defining success in a clinical trial is not necessarily a straightforward task, especially when the target population is critically ill patients where few agents have demonstrated effectiveness. This has been the case for trials of anticoagulation in patients with sepsis-associated disseminated intravascular coagulation (DIC), which have generally examined patients with severe sepsis but not specifically DIC. Limitations of existing studies include inadequate anticoagulant doses and delayed initiation of treatment. Furthermore, 28-day mortality has been adopted as the primary endpoint but is affected by a panoply of factors other than anticoagulant therapies and may not be the most relevant measure. Future trials must address several current limitations in order to improve our understanding of the role of anticoagulation in patients with sepsis-associated DIC.