Currently the treatment mainstay of sepsis is early and appropriate antibiotic therapy, accompanied by aggressive fluid administration, the use of vasopressors when needed and the prompt initiation of measures to support each failing organ. Activated protein C and hydrocortisone, when used accordingly can affect mortality. As the pathophysiologic events that take place during sepsis are being elucidated, new molecules that target each step of those pathways are being tested. However, a lot of those molecules affect various mediators of the sepsis cascade including inflammatory cytokines, cellular receptors, nuclear transcription factors, coagulation activators and apoptosis regulators. Over the last decade, a multitude of clinical trials and animal studies have investigated strategies that aimed to restore immune homeostasis either by reducing inflammation or by stimulating the innate and adaptive immune responses. Antibiotics, statins and other molecules with multipotent immunomodulatory actions have also been studied in the treatment of sepsis.