For a study, researchers sought to understand that nitric oxide (NO) generated vasodilation caused by inducible nitric oxide synthase (iNOS) may be the cause of sepsis-related hypotension has emerged. However, clinical testing with L-NAME demonstrated severe cardiac and pulmonary events and greater mortality in sepsis patients, in contrast to the expected pharmacological activity of a nitric oxide synthase (NOS) inhibitor. As a result, it was unknown what negative consequences NO may have on human shock and sepsis. Asymmetric dimethylarginine (ADMA), an endogenously produced NOS inhibitor synthesized as a host response to infection, may be significantly involved in the pathophysiology of sepsis and organ damage during ischemia-reperfusion, according to recent studies on the NO pathway. In addition to mitochondrial dysfunction, ADMA promotes oxidative stress, the generation of inflammatory cytokines, proinflammatory and prothrombotic endothelium conditions. Patients with sepsis often have high amounts of ADMA, and this chemical may have similar negative effects to L-NAME. Plasma ADMA levels and mortality in sepsis patients have been linked by numerous studies. Lowering ADMA has been demonstrated to reduce organ damage and increase survival in preclinical investigations employing sepsis and ischemia-reperfusion animal models. The preclinical research on ADMA “bed to bench” and the clinical outcomes with L-NAME led to the possibility of using ADMA reduction as a therapeutic strategy to postpone the beginning of organ damage and mortality in sepsis. This strategy could be investigated now that ADMA-selective lowering medications were available on the market.