Sepsis is a life-threatening condition caused by deregulation of the host's response to infection. Approaches to sepsis have evolved dramatically in recent decades, largely as a result of the rapid increase in knowledge about the epidemiology, physiopathology, and treatment of sepsis. In this context, a new international standard and definition of sepsis, the Third International Consensus Definition of Sepsis and Septic Shock (Sepsis-3), was introduced in 2016. The criteria were agreed by a task force of experts from the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. The main goal is to raise awareness among the professional community of this deadly disease, especially if not recognized and treated early. Sepsis-3 is also intended to serve as a benchmark for future preclinical and clinical research, development of new diagnostic methods, and treatment of patients with sepsis and septic shock. Many guidelines have been developed for the management of sepsis in children and adults. These guidelines emphasize early detection and aggressive management of patients with sepsis to improve outcomes. However, the circumstances in which the guidelines are intended to be used are important and can greatly affect their successful implementation. Therefore, in an attempt to create a sepsis policy that is relevant to both resource-poor and resource-rich environments, the resource levels of different environments are taken into account, and policies that cater to both resource-rich and poor regions of the world. Pediatric sepsis guidelines are designed to accommodate both the resources and capacities of countries with different under-5 mortality rates, and also consider resources for monitoring and treatment from community hospitals to tertiary care facilities. Additionally, since the final version in 2008, significant efforts have been expended to revise the Surviving Sepsis Campaign guidelines to include new evidence. While these efforts are laudable, adherence to these guidelines has yielded mixed results in both resource-poor and rich regions. Resources are therefore important for policy implementation, but factors other than resources can also hinder successful deployment. This manuscript addresses some of these issues. We review the benefits of adhering to sepsis guidelines, our published experience with compliance, the reasons for poor compliance, and some potential solutions to improve compliance and ultimately improve patient outcomes. There is no doubt that following the guidelines will lead to better results. In fact, following the American College of Critical Care Medicine (ACCM) guidelines for children increased her mortality by 30% when community hospital physicians followed initial resuscitation guidelines. In addition, a 27% reduction in mortality was observed in children treated according to ACCM guidelines, including synchronized central venous oxygen saturation (ScvO2) therapy in the intensive care unit. Adherence to sepsis guidelines in a Texas pediatric emergency department reduced the need for ventilators and vasoactive drugs, reducing mortality from 4% to 2.5%. Adherence to guidelines in children with sepsis reduced pediatric intensive care unit (PICU) stays by 57% in Boston, Boston, and increased adherence to sepsis guidelines in Utah resulted in mortality rates from 8.4% to 3.5 %. Sepsis, now defined as life-threatening organ dysfunction due to deregulation of the host's response to infection, was recently recognized by the World Health Organization as a global health priority. Sepsis causes or contributes to up to half of all hospital deaths in the United States.