Despite its known phytotoxicity, cadmium (Cd) is being added in most arable soils via different agricultural activities. Additionally, information is meager on the Cd-phytotoxicity mitigation strategies employing sustainable approaches. Essential plant nutrient calcium (Ca2+) and signaling molecule nitric oxide (NO) are known as the key regulators of plant biochemical and physiological processes under stress conditions. Though there exists a close functional synergism between Ca2+ and NO in plant stress tolerance, the role of either Ca2+ and/or NO has been explored in plant stress tolerance in isolated reports. Given this, in addition to briefly overviewing the availability, uptake, transport and toxicity (including impact on morpho-physio-logical traits, photosynthesis, oxidative stress, and genotoxicity), this paper aimed to highlight the general roles, transport, and signaling of Ca2+ and/or NO in plants, and appraises the literature available on their significance in improvements of plant growth, photosynthesis and control of oxidative stress under Cd stress. Effort was also made to present a crosstalk on Ca(2+ )and NO signaling, and the significance of its outcome in plant Cd-tolerance. (C) 2022 SAAB. Published by Elsevier B.V. All rights reserved.