Second generation antipsychotics (SGAs) have been implicated in the de novo emergence and exacerbation of obsessive-compulsive symptoms (OCS) in patients with schizophrenia. Among SGAs, clozapine, olanzapine, and risperidone are the most prominent agents associated with these sequelae, according to case reports. Comorbid OCS can impede recovery by compromising treatment benefits, medication compliance, and clinical prognoses. Previous reviews of SGA-induced OCS have predominantly focused on descriptive case reports, with limited attention paid toward experimental findings. To address this paucity of data, we sought to review the effects of SGAs on OCS in schizophrenia in the experimental literature, while addressing the role of different treatment (duration, dose, serum levels) and pharmacogenetic factors. Our findings suggest that clozapine confers the greatest risk of OCS in schizophrenia, with 20 to 28% of clozapine-treated patients experiencing de novo OCS, in addition to 10 to 18% incurring an exacerbation of pre-existing OCS. Clozapine can also yield full threshold obsessive-compulsive disorder (OCD), in some cases. Olanzapine is another high risk drug for secondary OCS which occurs in 11 to 20% of schizophrenic patients receiving olanzapine therapy. At this time, there is insufficient experimental evidence to characterize the effects of other SGAs on OCS. Despite some experimental support for the involvement of longer treatment duration and genetic factors in mediating drug-induced OCS, more research is needed to clearly elucidate these associations. Based on these results, schizophrenic patients should be routinely monitored for OCS throughout the course of SGA treatment, particularly when clozapine or olanzapine is administered.