SummaryThe role of ammonia in exercise-induced fatigue is reviewed. Implications for integrated activity of developing hyperammoneic states, caused by various precipitating conditions such as exercise, liver dysfunction, hypoxia, hyperoxia, and chemical poisoning are described.The central role of ammonia in diverse important metabolic pathways indicates its ubiquitous role in a spectrum of activity ranging from elite exhaustive performance of sportsmen and -women to life-threatening organ dysfunction. The action of ammonia and metabolites from associated pathways in producing seemingly dangerous short term conditions, but inducing possible long term protection against degenerative processes associated with ageing (free radical-induced cellular damage) indicate the paradoxical position of ammonia and its associated metabolic pathways for health and disease processes.