In the late 1990s, NO became an increasingly popular target of investigation in plants. As in mammals, NO fulfils a broad spectrum of signaling functions in pathophysiological processes in plants. Here, we summerize studies published in recent years that provide novel insights into the signaling functions of NO produced by plant cells exposed to abiotic stresses and biotic stress (pathogen-derived elicitors). Particularly, we report that NO emerges as a key messenger governing the overall control of Ca²⁺ homeostasis. Although the precise signaling functions of NO are poorly understood, its capacity to modulate Ca²⁺ homeostasis provides an extraordinary and remarkably effective way of conveying information.