Olanzapine is an atypical antipsychotic medication, previously expected to be safe in terms of hematological side effects and considered an alternative choice to clozapine in patients who develop hematotoxicities. However, since olanzapine was introduced to the market many case reports have been published revealing that it could cause hematoxicity. Some of these reports also indicated that olanzapine induced agranulocytosis. Therefore, we conducted a systemic review to explore and address this issue. Electronic database searches from 1998 to 2015 yielded 35 case reports of olanzapine-induced leukopenia and three related systematic reviews. The onset of leukopenia for the majority of these case reports followed in the first month of administration of olanzapine. Moreover, more than two third of these cases never developed drug-related leukopenia before the use of olanzapine. The ages of affected individuals were 16 to 83 years old and their races were African, Caucasian, Asian, Jewish and Mediterranean. The doses of olanzapine ranged from 2.5 to 30 mg. Interestingly, olanzapine was associated with third highest incidence of neutropenia among antipsychotics. The mechanism of olanzapine-induced neutropenia is still unknown, but could be similar to clozapine because of similar chemical composition. Therefore we recommend that the guidelines regarding olanzapine need to be reconsidered and closely monitored with patients being treated with olanzapine for hematological side effects.