The presence of heavy metals in soil is one of the major catastrophes that limits plant growth and productivity. Heavy metal stress causes excessive and uncontrolled production of Reactive Oxygen Species (ROS). ROS have severe damaging effects in plants, such as lipid peroxidation, damage to proteins, and alteration in various metabolic pathways of plants. Plants exposed to heavy metal stress develop various adaptive strategies. In response to heavy metal (HM) stress, plants release various signaling molecules that initiate a cascade of responses to confer tolerance to plants against heavy metal stress. One such molecule is nitric oxide (NO) that belongs to the class of reactive nitrogen species (RNS). NO is produced within plant cells under normal physiological conditions and is responsible for the regulation of various physiological and biochemical functions of plants. However, under HM stress, NO plays a significant role. NO either directly acts as a signaling molecule, upregulating/downregulating various enzymes, or it acts by activating the antioxidant machinery of plants, or it directly functions as an antioxidant in plants, thereby mitigating the negative effects of HM toxicity. The chapter discloses various pathways of NO synthesis as well as effects of NO (exogenous and endogenous) on plant machinery under HM stress. The chapter further discusses how NO helps in alleviating the negative effects of HM toxicity and counteracting the detrimental effects of HMs on plants.