On the Indian sub-continent, nearly 5,000 years ago, the domestication of the riverine buffalo-the incredible Asian dairy animal was initiated. It plays a versatile role in socio-economic upliftment of its owners from the rural agricultural communities in Asian, African, South American and a few European countries. Comparatively, buffaloes are lesser evolved and susceptible to infectious diseases than cattle. However, poor body thermoregulation and wallowing nature predisposed them to snail borne infections, especially tropical fasciolosis-an incessant major constraint on buffalo production and improvement programmes. This review article is an insight into the global prevalence, varied epizootiological factors, offers possible explanation to pathophysiological clinical signs, deleterious effects of the tropical liver fluke, involving hepato-biliary system, haemopoitic system, endocrine glands and their secretions, oxidative stress, altered metabolism and significant fall in food conversion efficiency with unaffected digestibility of nutrients. Besides, the authors have briefly discussed and reviewed the developments and significance of successful immunodiagnostic approaches for detecting and forecasting the disease during early pre-patency and feasibility of developing a cost effective immunoprotection strategies against tropical fasciolosis.