Sepsis is the result of the hosts’ response to an infectious agent, leading to organ dysfunction . It is a very common syndrome, estimated to have occurred in 48.9 million people in 2017, which represented an incidence of 677.5 (535.7–876.1) cases per 100,000 in the same year. It represents the cause of 1 in every 5 deaths annually worldwide, affecting especially small children, the elderly and people who live in low and middle-income countries. The largest contributors to sepsis incidence and mortality among all age groups were diarrheal diseases and lower respiratory infections, respectively. It has been endemic for centuries since infections from different foci have accompanied mankind. In modern medicine, much has been studied and learned about sepsis, but therapeutic measures are still very limited, especially when a noxious hyperinflammatory state takes place. The COVID pandemic has increased public awareness of organ damage induced by sepsis, which is positive per se; on the other hand, it is surprising that laypeople and even health professionals are taken by so much surprise, as organ dysfunction has been recognized a result of various infections for decades. It is as if SARS-CoV-2 is causing a previously unknown syndrome! The Surviving Sepsis Campaign (SSC) began as a collaboration of members of the European Society of Intensive Care Medicine (ESICM), the International Sepsis Forum (ISF), and the Society of Critical Care Medicine (SCCM), with an aim at improving the diagnosis, survival, and management of septic patients. Its conception was at the ESICM meeting in Barcelona in 2002, and the first published guidelines date - 2004. It is a very important initiative, as sepsis-associated mortality is unacceptably high, septic patients are seen routinely by all practicing physicians, who may not be aware of all treatment options, whilst innovation and research are ongoing and updating on those is crucial. Therefore, the aim of this editorial is to comment on the latest SSC guidelines, dated 2021. We shall point out the main novelties proposed in them.