Sterile inflammation is a type of inflammation that occurs in the absence of microbial infection, often due to tissue damage or cell death. It can resolve the initial insult or lead to disease. This review discusses the triggers and pathways involved in sterile inflammation and its impact on human health. Inflammation is crucial for host defense against pathogens and tissue repair. However, unresolved chronic inflammation can be harmful. Sterile inflammation is marked by the recruitment of neutrophils and macrophages and the production of pro-inflammatory cytokines such as TNF and IL-1. Examples of sterile inflammatory diseases include chronic inhalation of irritants, ischaemia-reperfusion injury, gout, and atherosclerosis. Pattern recognition receptors (PRRs) are involved in sensing both microbial and non-microbial signals, including damage-associated molecular patterns (DAMPs). DAMPs are endogenous molecules released during cell death or injury that can trigger inflammation. They include proteins like HMGb1, heat shock proteins, and purine metabolites. DAMPs can activate inflammatory pathways through various receptors, including TLRs, NLRP3, and AIM2 inflammasomes. The NLRP3 inflammasome is particularly important in sterile inflammation, as it can sense diverse stimuli such as asbestos, silica, and β-amyloid. Sterile inflammation is also involved in diseases like Alzheimer's and cancer. The role of PRRs in recognizing DAMPs is crucial for the immune response. The inflammasome, particularly the NLRP3 inflammasome, plays a key role in the production of IL-1β, a potent pro-inflammatory cytokine. The mechanisms by which DAMPs are recognized and processed by PRRs are still being studied. In addition to PRRs, DAMPs are recognized by specific receptors such as RAGE, which can activate inflammatory signaling pathways. The role of these receptors in disease pathogenesis is an area of ongoing research. Therapeutic strategies targeting IL-1 and TLRs have shown promise in treating sterile inflammatory disorders. However, the optimal targets and contexts for treatment remain to be determined. Understanding the mechanisms of sterile inflammation is essential for developing effective treatments for various human diseases.Sterile inflammation is a type of inflammation that occurs in the absence of microbial infection, often due to tissue damage or cell death. It can resolve the initial insult or lead to disease. This review discusses the triggers and pathways involved in sterile inflammation and its impact on human health. Inflammation is crucial for host defense against pathogens and tissue repair. However, unresolved chronic inflammation can be harmful. Sterile inflammation is marked by the recruitment of neutrophils and macrophages and the production of pro-inflammatory cytokines such as TNF and IL-1. Examples of sterile inflammatory diseases include chronic inhalation of irritants, ischaemia-reperfusion injury, gout, and atherosclerosis. Pattern recognition receptors (PRRs) are involved in sensing both microbial and non-microbial signals, including damage-associated molecular patterns (DAMPs). DAMPs are endogenous molecules released during cell death or injury that can trigger inflammation. They include proteins like HMGb1, heat shock proteins, and purine metabolites. DAMPs can activate inflammatory pathways through various receptors, including TLRs, NLRP3, and AIM2 inflammasomes. The NLRP3 inflammasome is particularly important in sterile inflammation, as it can sense diverse stimuli such as asbestos, silica, and β-amyloid. Sterile inflammation is also involved in diseases like Alzheimer's and cancer. The role of PRRs in recognizing DAMPs is crucial for the immune response. The inflammasome, particularly the NLRP3 inflammasome, plays a key role in the production of IL-1β, a potent pro-inflammatory cytokine. The mechanisms by which DAMPs are recognized and processed by PRRs are still being studied. In addition to PRRs, DAMPs are recognized by specific receptors such as RAGE, which can activate inflammatory signaling pathways. The role of these receptors in disease pathogenesis is an area of ongoing research. Therapeutic strategies targeting IL-1 and TLRs have shown promise in treating sterile inflammatory disorders. However, the optimal targets and contexts for treatment remain to be determined. Understanding the mechanisms of sterile inflammation is essential for developing effective treatments for various human diseases.