Quetiapine is a novel and atypical antipsychotic agent with serotonin 5-HT2A antagonism higher than D2 blockade. However, it has the lowest affinity for serotonin receptors among atypical antipsychotics. Besides its D2 blockade, it is not as great as seen with risperidone and olanzapine and is even less than that of clozapine. Open-label and controlled trials suggest efficacy of quetiapine as an adjunct therapy in patients with obsessive-compulsive disorder, refractory to treatment with selective serotonin reuptake inhibitors. There is one report of quetiapine exacerbating obsessive-compulsive symptoms (OCS). We report 5 cases with bipolar I disorder (n = 3), psychotic depression (n = 1), and schizophrenia (n = 1) in which quetiapine produced de novo OCS. The underlying pathogenetic mechanisms and the risk factors for this action of quetiapine and of atypical antipsychotics, in general, are not yet known. The description of 5 patients with different diagnoses supports the issue of OCS exacerbation or induction with atypical antipsychotics. Clinicians' awareness and close monitoring of the patients is warranted.