The article reviews the mechanisms by which dying cells alert the immune system to danger. When cells die in vivo, the host's immune system detects this event and responds to investigate the nature of the cell death. If the death is due to natural causes, there is little threat to the organism, and the focus is on removing the dead cells. However, if the death is due to violence or disease, both defense and repair mechanisms are activated. The immune system has evolved to respond to non-infectious cell death, which is considered a universal sign of danger. This process, known as the danger hypothesis, was proposed by Matzinger in 1994. The article discusses the evidence supporting the concept that the immune system can sense primary or secondary necrotic cell death and respond with innate and adaptive immune responses. It highlights the role of damage-associated molecular patterns (DAMPs) released from dying cells, which act as endogenous adjuvants to stimulate the immune system. The article also explores the inflammatory response to cell death and its potential costs to the host, emphasizing the need to understand these responses to develop therapeutic interventions.The article reviews the mechanisms by which dying cells alert the immune system to danger. When cells die in vivo, the host's immune system detects this event and responds to investigate the nature of the cell death. If the death is due to natural causes, there is little threat to the organism, and the focus is on removing the dead cells. However, if the death is due to violence or disease, both defense and repair mechanisms are activated. The immune system has evolved to respond to non-infectious cell death, which is considered a universal sign of danger. This process, known as the danger hypothesis, was proposed by Matzinger in 1994. The article discusses the evidence supporting the concept that the immune system can sense primary or secondary necrotic cell death and respond with innate and adaptive immune responses. It highlights the role of damage-associated molecular patterns (DAMPs) released from dying cells, which act as endogenous adjuvants to stimulate the immune system. The article also explores the inflammatory response to cell death and its potential costs to the host, emphasizing the need to understand these responses to develop therapeutic interventions.