The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is ubiquitously expressed in almost all tissues and organs of the body with the highest distribution in the immune cells of monocyte-macrophage origin. Classically, P2X7 receptor is involved in apoptotic cell death, and it is well known that extracellular ATP ligation to this purinergic receptor serves as an important secondary stimulus, which is also considered as danger signal for the interleukin (IL)-1β cleavage and secretion from pro-inflammatory cells. More recently, however, there has been substantial evidence of additional roles for the P2X7 receptor, both in innate immune response and as an adaptive link, including T-cell activation in a chronic state of inflammation. Also, compelling evidences have revealed an important role for ectonucleotidases as ATP-consuming enzymes in the control and fine-tuning of P2X7 function by regulating the time, concentration, and availability of ATP during infection-driven inflammation. This review focuses on the current evidences for P2X7 receptor involvement in the initial stages of inflammation, as well as for its role in acute and chronic stages of infection. Here, we also highlight the role of ectonucleotidase family in the control of P2X7 function, including the initial and resolution phases of inflammation.