Glycine was first used as an augmenting treatment in schizophrenia close to 30 years ago in a few small open-label clinical trials used at doses between 5 and 25 g per day (138, 143–145). In subsequent controlled trials, 60 g of glycine augmented with first-generation or second-generation antipsychotic medication was reported to improve not only the negative symptoms (146–150), but also cognitive symptoms (147, 148, 150) and the depressive symptoms of the illness (148). Glycine is not able to cross the blood-brain barrier easily as it has no specific amino acid transporter, so higher doses must be used that impacts patients' tolerability to glycine. The benefits reported of using glycine as an augmenting treatment to antipsychotic medications to improve the cognitive and negative symptoms domains of the illness has since been disputed. In a subsequent review, glycine was found to have moderate effect in reducing negative symptoms and it was uncertain whether it had any benefit at improving cognitive symptoms (151). The multicentre Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST), found no significant differences between glycine and placebo at improving the negative or cognitive symptom domains of the illness (152). Overall, glycine may be beneficial for those patients that have treatment resistance specific to the negative and cognitive symptom domains; (153) however it has not been a beneficial augmenting strategy in patients with TRS on clozapine (154).