<p>Plants, being sessile, have evolved intricate defense mechanisms to cope up with biotic stresses. These defense mechanisms are often regulated by complex signalling pathways and their crosstalk. Secondary messengers such as Ca²⁺, H₂O₂ and other Reactive Oxygen Species (ROS) are key mediators and act concomitantly in receiving extracellular signals and generating specific defense responses through long/short distance signal transmission. The spatiotemporal regulation of Ca²⁺ concentrations, coordinated by various cellular components, is crucial for initiating specific defense responses within the cell. The decoding and relay of Ca²⁺ signals are mediated by Ca²⁺ sensors and responder proteins, which trigger downstream cellular responses. Additionally, ROS are generated in response to various biotic stresses, which serve as key players in the complex network of signalling events and the interplay between ROS and Ca²⁺-signalling pathways intensify each other for fine-tuning the signalling network in inciting plant defense response. Ca²⁺-sensor proteins act as potential molecular switches, which link these signalling pathways as well as molecular machinery responsible for synergistic interaction between ROS and Ca²⁺-signals. In this review, we briefly touch on the crosstalk of Ca²⁺ and ROS signalling pathways during defense responses to underscore the complexity of the cellular signalling network. Understanding these signalling pathways along with their crosstalk and the molecular mechanisms underlying plant immune response, is crucial for developing strategies to enhance crop resilience and productivity.</p>