Sepsis is a serious condition where the body responds improperly to an infection. Every 2.8 seconds, someone dies of sepsis globally, yet no direct therapies exist beyond supportive care. Many clinical trials have investigated the role of Tumor Necrosis Factor (TNF) as a potential therapeutic target, but anti-TNF therapy has not proven to be a breakthrough in the sepsis field. Therefore, understanding how TNF triggers this devastating condition could be of help for millions of people worldwide.