Extracellular ATP and other nucleotides are important autocrine/paracrine mediators that stimulate purinergic receptors and regulate diverse processes in the normal lungs. They are also associated with pathogenesis of a number of respiratory diseases and clinical complications including acute respiratory distress syndrome and ventilator induced lung injury. Mechanical forces are major stimuli for cellular ATP release but precise mechanisms responsible for this release are still debated. The present review intends to provide the current state of knowledge of the mechanisms of ATP release in the lung. Putative pathways of the release, including the contribution of cell membrane injury and cell lysis are discussed addressing their strength, weaknesses and missing evidence that requires future study. We also provide an overview of the recent technical advances in studying cellular ATP release in vitro and ex vivo. Special attention is given to new insights into lung ATP release obtained with the real-time luminescence ATP imaging. This includes recent data on stretch-induced mechanosensitive ATP release in a model and primary cells of lung alveoli in vitro as well as inflation-induced ATP release in airspaces and pulmonary blood vessels of lungs, ex vivo.