Antipsychotic-induced obsessive-compulsive symptoms (OCS) are common clinical entities in patients with schizophrenia. Second-generation antipsychotics, particularly high anti-serotonergic effects, are associated with an increased risk of developing OCS. Limited evidence shows that single nucleotide polymorphisms in glutamate transporter gene SLC1A1 and its interactions with DLGAP3 and GRIN2B may play a role in the onset of antipsychotic-induced OCS. However, these preliminary findings are insufficient to conclude with a genetic background of antipsychotic-induced OCS. There are no significant demographic variables except for few positive findings of paternal age and male sex, but sociodemographic risk factors for pure OCD should be investigated. Regarding other clinical variables, OCS are positively correlated with the severity of depression, psychosis, and disability. Neuroimaging findings highlight alterations in activation and connectivity of orbitofrontal cortex, limbic structures (amygdala and thalamus), and the cortico-striatal-thalamo-cortical circuitry. This chapter goes on to discuss the relationship between antipsychotic-induced OCS and several risk factors including altered brain connectivity, as well as to propose a pathophysiological model for conceptualization of the phenomenon.