Sulfonation plays a crucial role in regulating the biological actions of numerous endogenous and exogenous compounds, such as medicines, harmful substances, hormones, and neurotransmitters. Many xenobiotics and endogenous chemicals undergo sulfonation reactions that can either activate or inactivate them. At least 10 functional genes in humans are involved in the cytosolic sulfotransferase (SULT) superfamily that catalyses the process. There is a possibility that arylsulafatase in the endoplasmic reticulum can counteract this process in healthy cells. The availability of the co-substrate/donor molecule 3'- phosphadensoine-5-phosphosulfate (PAPS) and the transport mechanisms that allow sulfated conjugates to enter and leave cells play a role in regulating sulfonation under physiological settings. There is evidence that genetic variations in each of the aforementioned pathways contribute to the observed variation in the response of individuals to various medications and harmful substances. Sulfonation plays a pivotal role in endocrine regulation, affecting not only the receptor activity of oestrogens and androgens but also steroid production and the metabolism of catecholamines and iodothyronines. Since SULTs are extensively expressed in the human foetus, sulfonation, a critical process in the body's defence against harmful substances, may play a significant role in early development. Sulfonation, as the final stage in the activation of numerous dietary and environmental substances to highly reactive hazardous intermediates implicated in carcinogenesis, is similar to many Phase I and Phase II processes.