Pyroptosis is a pro-inflammatory form of regulated cell death and is dependent on the enzymatic activity of inflammatory proteases that belong to the family of cysteine-dependent aspartate-specific proteases (caspases). Pyroptosis is morphologically, mechanistically, and pathophysiologically distinct from other forms of cell death, including apoptosis and necrosis. Pyroptosis is characterized by rapid plasma membrane rupture, with the consequent release of intracellular contents and pro-inflammatory mediators, including interleukin (IL)-1β, IL-18, and the alarmin HMGB-1.Recent studies have shown that pyroptosis may be involved in atherosclerosis and play an important role in atherosclerotic lesion instability. Here, we review the progress made in understanding the morphological, molecular, and pathophysiological mechanisms of pyroptosis and its potential role in atherosclerosis.