India is appreciably striving from underdeveloped to developing and yet a step closer to a developed nation. The country’s economy is best supported by its increasing share of the world’s fish production. Our sustained efforts to diversify and increase fish production have revolutionized the production trend. The biggest realisation from intensive research indicates that stress is the driver of every disease. Our understanding regarding fish immunity and environmental stress factors is that the invariable interaction of a multitude of factors surrounding fish is influenced differently, regulated by its physiological status, life stage, species, stocking density, nature and magnitude of stress. However, opportunistic pathogens overwhelm the immunologically compromised conditions, proliferate and establish infection when the H-P-E triad fails. Noninfectious diseases are often overlooked and masked due to their non-communicable/non-transmissible nature. The physicochemical parameters, as well as environmental pollutants, also play roles in dictating noninfectious diseases. In addition, the complex and dynamic interaction between these parameters is difficult to understand and probe. The nonspecific symptoms and clinical signs of pathogenic infection and noninfectious diseases are another challenge for pathologists. In a broad sense, lesions, imbalances, deformities, anorexia, anaemia, weight loss and respiratory failure may be the prominent manifestations of noninfectious diseased fishes. The omnipresent risk factors and threats from the environment are an ever-continuing process. Either deliberately or unknowingly, anthropogenic activities directly contribute to aquatic menace in the form of infectious and noninfectious diseases. Hence, constraints are many day by day in aquaculture, which warrants a one health programme and more understanding of epidemiological studies in order to prevent and diagnose diseases appropriately. The affirmation may be apparently impractical, but a reduction of such hitch factors from the culture system not only makes fish immunologically uncompromised but also limits the spread of pathogens and disease epidemiology.