The mechanisms of ammonia toxicity are still poorly understood, although hyperammonemia can cause symptoms similar to those observed in patients with autism spectrum disorders (ASD). Understanding the molecular pathways involved in ammonia neurotoxicity may possibly explain the reasons for the formation of brain abnormalities in ASD, and also open prospects for reducing ammonia exposure. In the first part of this review, we consider the mechanisms of ammonia toxicity, including the effects on the developing nervous system. We focus on the role of hyperammonemia in the modulation of neurotransmission systems and the development of neuroinflammation. In the second part of the review, we highlight the link between hyperammonemia and autism. We discuss changes in ammonia metabolism in animals with autism models and in patients with ASD, and possible causes of such abnormalities.