Summary Toll/interleukin‐1 receptor (TIR) domain‐containing immune receptors are crucial for plant immunity, with recent advancements highlighting the enzymatic functions of TIR domains and their production of signaling molecules. TIR‐catalyzed compounds interact with receptors to form functional modules that trigger the oligomerization of helper proteins, regulating Ca 2+ influx and downstream signaling. Moreover, TIR proteins have been recognized not only as intracellular receptors for pathogenic effectors but also for their broader immune signaling capabilities. Although typical TIR‐containing proteins are missing in monocots, both monocots and dicots exhibit conserved mechanisms in utilizing TIR proteins for immune signaling, underscoring their significance across diverse plant lineages. This review consolidates recent findings on TIR‐initiated signaling, its intricate roles, and the fine‐tuned regulatory mechanisms governing plant defense.