Contamination of the soil with cadmium (Cd) presents serious hazards to plant growth, ecosystem harmony, and human health. Plants have evolved various mechanisms to address Cd toxicity, such as sequestration, chelation, and antioxidant defense systems. Knowledge of these mechanisms is an important requisite for the development of strategies to relieve Cd stress in plants. More recent studies also implicate the role of the neurotransmitter 5-hydroxytryptamine (serotonin) in enabling Cd mitigation behavior in plants. Beyond its well-known role in animals, serotonin has emerged as a vital signaling molecule in plants, contributing to stress responses and regulatory pathways. This review focuses on the different Cd tolerance mechanisms in plants and describes the role of serotonin in protection against Cd toxicity. Moreover, it investigates how serotonin interacts with other signaling molecules to coordinate Cd stress responses. Understanding the intricate network of Cd tolerance mechanisms and the involvement of serotonin is essential for developing effective strategies to combat Cd stress in plants and improve environmental quality.