Adenosine, a key endogenous molecule, regulates tissue function through the activation of four G-protein-coupled receptors: A1, A2A, A2B, and A3. These receptors are expressed by immune cells and play crucial roles in modulating immune and inflammatory responses. Recent studies have highlighted the potential therapeutic use of adenosine-receptor-based therapies in treating infections, autoimmunity, ischemia, and degenerative diseases. Adenosine accumulation in response to metabolic stress and cell damage is a protective mechanism that helps maintain homeostasis. The signaling pathways of adenosine receptors include G protein coupling, adenylyl cyclase inhibition, and activation of various kinases. Macrophages, dendritic cells, neutrophils, mast cells, and lymphocytes are key immune cells that respond to adenosine through these receptors. A2A receptors are particularly important in modulating cytokine production and immune cell functions. In asthma, chronic obstructive pulmonary disease (COPD), arthritis, sepsis, inflammatory bowel disease, and wound healing, adenosine and its receptors play significant roles. A2A receptor agonists have shown promise in animal models and clinical trials for treating these conditions, while A2B receptor antagonists may be effective in managing asthma and COPD. Overall, targeting adenosine receptors offers a promising therapeutic approach for inflammatory and immune diseases.Adenosine, a key endogenous molecule, regulates tissue function through the activation of four G-protein-coupled receptors: A1, A2A, A2B, and A3. These receptors are expressed by immune cells and play crucial roles in modulating immune and inflammatory responses. Recent studies have highlighted the potential therapeutic use of adenosine-receptor-based therapies in treating infections, autoimmunity, ischemia, and degenerative diseases. Adenosine accumulation in response to metabolic stress and cell damage is a protective mechanism that helps maintain homeostasis. The signaling pathways of adenosine receptors include G protein coupling, adenylyl cyclase inhibition, and activation of various kinases. Macrophages, dendritic cells, neutrophils, mast cells, and lymphocytes are key immune cells that respond to adenosine through these receptors. A2A receptors are particularly important in modulating cytokine production and immune cell functions. In asthma, chronic obstructive pulmonary disease (COPD), arthritis, sepsis, inflammatory bowel disease, and wound healing, adenosine and its receptors play significant roles. A2A receptor agonists have shown promise in animal models and clinical trials for treating these conditions, while A2B receptor antagonists may be effective in managing asthma and COPD. Overall, targeting adenosine receptors offers a promising therapeutic approach for inflammatory and immune diseases.