CD39 and CD73 are key enzymes in the purinergic system that regulate immune and inflammatory responses by converting ATP and ADP to AMP and then to adenosine. This process shifts immune cells from a pro-inflammatory state to an anti-inflammatory one. The CD39/CD73 pathway dynamically adjusts based on the pathophysiological context and plays a critical role in various diseases, including infections, autoimmune disorders, atherosclerosis, ischemia-reperfusion injury, and cancer. These enzymes are emerging as important therapeutic targets for managing these conditions. CD39 and CD73 are expressed on various immune cells, including Tregs, neutrophils, monocytes, macrophages, and dendritic cells, and their activity is regulated by cytokines, oxidative stress, and hypoxia. The CD39/CD73 pathway influences immune cell function by modulating the extracellular purinergic environment, affecting cell adhesion, cytokine release, and immune suppression. In Tregs, CD39 and CD73 contribute to immunosuppression by generating adenosine, which activates A2A receptors on effector T cells, reducing inflammation. In neutrophils, CD39 and CD73 regulate the balance between pro-inflammatory and anti-inflammatory responses. In macrophages, CD39/CD73 influence the differentiation into M1 and M2 phenotypes, with M2 macrophages generating an adenosine-rich environment that promotes anti-inflammatory effects. In endothelial cells, CD39/CD73 help maintain vascular homeostasis by converting the extracellular environment from a prothrombotic to an antithrombotic state. In infections, pathogens can exploit CD39/CD73 to evade immune detection, while in some cases, these enzymes can limit infection and inflammation. In autoimmune diseases like multiple sclerosis and rheumatoid arthritis, CD39/CD73 regulate immune tolerance and inflammation. In cancer, CD39/CD73 contribute to immunosuppression, promoting tumor growth and metastasis. Pharmacological modulation of CD39 and CD73 is being explored as a potential therapeutic strategy for various diseases.CD39 and CD73 are key enzymes in the purinergic system that regulate immune and inflammatory responses by converting ATP and ADP to AMP and then to adenosine. This process shifts immune cells from a pro-inflammatory state to an anti-inflammatory one. The CD39/CD73 pathway dynamically adjusts based on the pathophysiological context and plays a critical role in various diseases, including infections, autoimmune disorders, atherosclerosis, ischemia-reperfusion injury, and cancer. These enzymes are emerging as important therapeutic targets for managing these conditions. CD39 and CD73 are expressed on various immune cells, including Tregs, neutrophils, monocytes, macrophages, and dendritic cells, and their activity is regulated by cytokines, oxidative stress, and hypoxia. The CD39/CD73 pathway influences immune cell function by modulating the extracellular purinergic environment, affecting cell adhesion, cytokine release, and immune suppression. In Tregs, CD39 and CD73 contribute to immunosuppression by generating adenosine, which activates A2A receptors on effector T cells, reducing inflammation. In neutrophils, CD39 and CD73 regulate the balance between pro-inflammatory and anti-inflammatory responses. In macrophages, CD39/CD73 influence the differentiation into M1 and M2 phenotypes, with M2 macrophages generating an adenosine-rich environment that promotes anti-inflammatory effects. In endothelial cells, CD39/CD73 help maintain vascular homeostasis by converting the extracellular environment from a prothrombotic to an antithrombotic state. In infections, pathogens can exploit CD39/CD73 to evade immune detection, while in some cases, these enzymes can limit infection and inflammation. In autoimmune diseases like multiple sclerosis and rheumatoid arthritis, CD39/CD73 regulate immune tolerance and inflammation. In cancer, CD39/CD73 contribute to immunosuppression, promoting tumor growth and metastasis. Pharmacological modulation of CD39 and CD73 is being explored as a potential therapeutic strategy for various diseases.