Plants have evolved a set of finely regulated mechanisms to respond to various biotic stresses. Transient changes in intracellular calcium (Ca2+) concentration have been well documented to act as cellular signals in coupling environmental stimuli to appropriate physiological responses with astonishing accuracy and specificity in plants. Calmodulins (CaMs) and calmodulin‐like proteins (CMLs) are extensively characterized as important classes of Ca2+ sensors. The spatial‐temporal coordination between Ca2+ transients, CaMs/CMLs and their target proteins is critical for plant responses to environmental stresses. Ca2+‐loaded CaMs/CMLs interact with and regulate a broad spectrum of target proteins, such as ion transporters (including channels, pumps, and antiporters), transcription factors, protein kinases, protein phosphatases, metabolic enzymes and proteins with unknown biological functions. This review focuses on mechanisms underlying how CaMs/CMLs are involved in the regulation of plant responses to diverse biotic stresses including pathogen infections and herbivore attacks. Recent discoveries of crucial functions of CaMs/CMLs and their target proteins in biotic stress resistance revealed through physiological, molecular, biochemical, and genetic analyses have been described, and intriguing insights into the CaM/CML‐mediated regulatory network are proposed. Perspectives for future directions in understanding CaM/CML‐mediated signalling pathways in plant responses to biotic stresses are discussed. The application of accumulated knowledge of CaM/CML‐mediated signalling in biotic stress responses into crop cultivation would improve crop resistance to various biotic stresses and safeguard our food production in the future.