The escalating demand for aquatic food products has driven the rapid intensification of aquaculture worldwide, simultaneously increasing the risk of infectious disease outbreaks caused by bacteria, fungi, viruses, and parasites. Chemotherapeutic intervention has become an indispensable component of disease management, playing a vital role in controlling infections and safeguarding aquaculture production. This review systematically classifies the principal groups of chemotherapeutic agents used in aquaculture, including antibacterials, antifungals, antiparasitic agents, antiviral compounds, anaesthetics, and disinfectants, with emphasis on their mechanisms of action, spectrum of activity, and practical applications in cultured fish and shellfish. The article also discusses the major routes of drug administration, including immersion, oral administration through medicated feed, injection, gavage, and topical application, highlighting their suitability according to disease type, fish size, and production system. Furthermore, it underscores the importance of the judicious use of chemotherapeutic agents to minimize the development of antimicrobial resistance (AMR), reduce drug residues in aquatic food products, and prevent environmental contamination. In addition, the article highlights emerging alternatives such as vaccines, probiotics, and immunostimulants as sustainable approaches for disease prevention and health management in aquaculture.