The care of the critically ill patient in low-resource settings is challenging because of many factors, including limitations in the existing infrastructure, lack of disposables, and low numbers of trained healthcare workers. Although cost constraints in low-resource settings have traditionally caused critical care to be relegated to a low priority, ethical issues and the potential for mitigation of the lethal effects of often reversible acute conditions, such as sepsis and traumatic hemorrhage, argue for prudent deployment of critical care resources. Given these challenges, issues that require prioritization include timely and reliable delivery of evidence-based or generally accepted interventions to acutely ill patients before the development of organ failure, context-specific adaptation and evaluation of clinical evidence, and sustained investments in quality improvement and health systems strengthening. Specific examples include fluid resuscitation algorithms for patients with sepsis and reliable, low-cost, high-flow oxygen concentrators for patients with pneumonia. The lessons from new research on clinical management and sustainable education and quality improvement approaches will likely improve the care of critically ill patients worldwide.