The purpose of this study was to conduct a systematic review of the scientific-medical literature to identify, appraise, and synthesize the human evidence for the effects of omega-3 fatty acids on mental health. While the intention was to evaluate the spectrum of psychiatric disorders or conditions (i.e., behavior or symptoms which, while their consequences could be serious, do not warrant receipt of a formal psychiatric diagnosis), certain foci were beyond the scope of the review. At the same time, a mental health disorder or condition did not require extant animal or basic science data or models to justify the investigation of their evidence. Nevertheless, justification for the study of two disorders exists in the literature: depression and schizophrenia. The mechanism by which diet may affect health, including depression or cardiovascular disease, has been thought to involve low levels of omega-3 fatty acid content in biomarkers (e.g., red blood cells RBCs]). An omega-3 fatty acid deficiency hypothesis of depression has been put forward, which has helped justify treatment with omega-3 fatty acid supplementation. The membrane phospholipid hypothesis of schizophrenia has been proposed in an attempt to develop a model explaining its etiology. It describes the presumed biochemical dynamics underpinning a neurodevelopmental theory. Some of the evidence used to support this perspective suggests the existence of phospholipid and polyunsaturated fatty acid (PUFA) metabolic abnormalities in schizophrenia. It has been posited that modifications to diet could mitigate or even aggravate an underlying abnormality of phospholipid metabolism. However, the present review was not conducted to test these hypotheses. Rather, the rationale for this 2-year project investigating the possible health benefits of omega-3 fatty acids was to systematically review the evidence to aid in the development of a research agenda. Nevertheless, these emerging models regarding depression and schizophrenia do suggest plausible bases for the use of omega-3 fatty acids to treat or prevent these psychiatric disorders.