This essay summarised the most encountered chemical sulfation methods of small molecules (Figure ). Traditional sulfation reactions have relied on sulfuric acid derivatives. Sulfation reaction using sulfur trioxide amine/amide complexes was the most used method for alcoholic or phenolic groups in carbohydrates, steroids, proteins, and aliphatic or alicyclic scaffolds. Despite the effectiveness of these methods, they suffer from some issues such as multiple-purification steps reactions, toxicity issues (eg pyridine contamination), purification challenges, stoichiometric excess of reagents which leads to increase of a reaction cost, and intrinsic stability issues of both the reagent and product.