Inflammasomes are cytoplasmic macromolecular complexes playing an important role in sensing exogenous and endogenous stimuli. Inflammasome activation leads to IL-1β and IL-18 secretion and pyroptosis. The concept of non-self recognition triggering inflammasome activation has been well-established for myeloid cells. However, increasing evidence suggests the presence of functional inflammasome or inflammasome-related components in lymphocytes. Dysregulated expression of inflammasome contributes to the development of many diseases, including cardiovascular, infectious, neurodegenerative diseases and cancer. Multiple clinical trials are being conducted to assess drugs targeting various inflammasome components. This review discusses current knowledge on inflammasome activation in T, B and NK cells and explores their potential as therapeutic targets. Further understanding inflammasome and pyroptotic pathways in lymphocytes may have implications in the development of novel immunotherapeutic strategies.