Abstract Background: The association between schizophrenia and the metabolic syndrome is frequent and well studied in the literature. The risk of induction of this syndrome by atypical antipsychotic drugs in patients with schizophrenia is well known. The aim of this study is to evaluate the association between schizophrenia and the metabolic syndrome independently from the risk of induction of this syndrome by atypical antipsychotic drugs. Methods: A search was done via MedLine for articles written in English or in French, published between 1988 (date of establishment of the first definition of the metabolic syndrome) and December 2010, using the following terms: "metabolic syndrome", "dyslipidemia", "glucose intolerance" or "diabetes" in association with "schizophrenia" or "psychosis". Results: Evidence on the existence of a relationship between severe mental disorders such as schizophrenia and the metabolic syndrome exist before the introduction of the first antipsychotic drug in 1952. Other than atypical antipsychotic drugs, psychotropic drugs such as antidepressants and mood stabilizers, which can be frequently given to patients with schizophrenia, are also incriminated in the induction of some of the components of the metabolic syndrome. Patients suffering from schizophrenia present a tendency toward having an abdominal obesity, an excess of circulating cortisol as a consequence of this central obesity and a hepatic insulin resistance. Their reaction to continuous stress hyper activates the hypothalamo-pituitary-adrenal axis. Some genetic features are common to both schizophrenia and metabolic syndrome. Finally, the lifestyle of patients with schizophrenia is full of risk factors that can aggravate the metabolic syndrome such as sedentarism, smoking habits, low socio-economic status, low adherence to medical care etc. Conclusion: The relationship between schizophrenia and the metabolic syndrome seems to contain, in the current medical literature, more than the simple fact related to the intake of atypical antipsychotic drugs.