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Disposal of waste products accumulated during metabolic processes is integral to the health of any living organism. Disposal of excess nitrogen and ammonia is no exception. Although nitrogen is essential for growth and maintenance in animals, an excess of some nitrogenous compounds can quickly lead to toxicity and death. Because of the correlation between ammonia accumulation and clinical disease, it is important for veterinary clinicians to understand the physiological mechanisms used to dispose of nitrogen and ammonia. Therefore, the purposes of this article are to review ammonia metabolism, the urea cycle, and the clinical implications of urea cycle dysfunction in diseases of companion animals.