Sepsis and septic shock are frequently complicated by disseminated intravascular coagulation (DIC), which decreases the survival rate of patients with sepsis. In the past, large international randomized controlled trials (RCTs) using physiological anticoagulants for sepsis-induced DIC were not performed; however, RCTs have been conducted for sepsis and/or septic shock. In these trials, physiological anticoagulants did not show any beneficial effects compared with placebo for the treatment of sepsis and/or septic shock. In Japan, DIC treatments using antithrombin (AT) and/or recombinant human soluble thrombomodulin (rhTM) are common for patients with sepsis-induced DIC. Recently, large propensity score analyses demonstrated that AT and rhTM improved survival in patients with sepsis-induced DIC. Furthermore, post hoc analyses and meta-analyses that selected patients with sepsis-induced DIC from the previous large international RCTs indicated that physiological anticoagulants improved survival without increasing the associated sepsis-induced DIC bleeding. DIC treatments, such as AT and rhTM, may demonstrate beneficial effects when they are targeted at patients with sepsis-induced DIC only.