Indian catfish, Heteropneustes fossilis (Bloch), is a freshwater species of significant aquacultural and commercial value in South Asia. However, the production of this species has been hampered by microbial infections, leading to significant economic losses. This paper reviews the current understanding of microbial infections in H. fossilis, focusing on the types of pathogens involved, their impact on fish health, and possible treatment methods. The study also explores the advancements in diagnostic techniques and preventive strategies that could mitigate the impact of these infections. Recent developments in immunostimulants, probiotics, and nanotechnology-based treatments are also discussed. The paper also emphasizes the identification of biomarkers and the possible progress they portend in enhancing the omics approach. Immunostimulants are substances that enhance the immune system’s ability to fight infections. In H. fossilis, immunostimulants such as β-glucans, chitosan, and herbal extracts have been studied for their ability to boost the fish’s innate immunity.