Clozapine is the drug of choice for the treatment of refractory schizophrenia. However, since 1975, clozapine is known to cause granulocyte deficiency. In the clozapine screening guidelines, a white blood cell count is mandatory. In the last 20 years, after the reintroduction of clozapine, three additional side effects of it, namely diabetic ketoacidosis, gastrointestinal hypokinesia and myocarditis, have been documented but have not been written into the screening guidelines. The aim of this review was to determine whether the update of the clozapine side effect screening guidelines was evidence-based. We searched MEDLINE or PubMed using the keywords clozapine, granulocyte deficiency, diabetic ketoacidosis, and gastrointestinal hypokinesia and collected English-language literature published from 1976 to 2010 on the incidence of the four side effects of clozapine. A total of 16 studies that could provide reliable data were included. We compared the 1-year incidence, mortality in the entire study population with mortality in affected patients. When rates reflected a longer observation period, these rates were recalculated to obtain 1-year incidence rates. The results showed that the incidence of granulocyte deficiency due to clozapine ranged from 3.8 per 1000 to 8.0 per 1000. The mortality rate was 0.1‰ to 0.3‰, and the lethality rate was 2.2‰ to 4.2‰. The calculated incidence of diabetic ketoacidosis was 1.2‰ to 3.1‰, and the lethality rate was 20% to 31%. The incidence of gastrointestinal hypokinesia was 4‰ to 8‰, with a lethality rate of 15% to 27.5%. Differences in the incidence between Australia and other countries (7‰ to 34‰V0.07‰ to 0.6‰) have led to the lack of a common method for monitoring this side effect. Of the 3 side effects studied, a reduction in mortality to granulocyte deficiency levels is possible for 2 of the 3, diabetic ketoacidosis and gastrointestinal hypokinesia. For this reason, screening guidelines need to be modified and early detection of hyperglycemia that occurs during treatment (which may progress through diabetes to diabetic ketoacidosis) requires mandatory monthly fasting glucose testing. To prevent gastrointestinal hypokinesia and its complications, clinicians should be required to monitor weekly or prescribe standard light laxatives for prevention at the same time.