Electrophilic and nucleophilic reactions of benzocaine are the most common procedures to construct a library of benzocaine derivatives, which have promising features that could be correlated with their biological activities. This critical review documents the synthesis of benzocaine and its reactions. These reactions provide structures with antimicrobial, anti-inflammatory, anticancer activities, as a result of inhibition of acetylcholine esterase, cyclooxygenase, fatty acid transport protein, and human immunodeficiency virus. Recent studies presented some bioactive modification of benzocaine as leteprinim for the treatment of neurodegenerative disorders such as Alzheimer’s, Parkinson’s disease, stroke and (-)-vincadifformine as antitumor.