Individuals with OCD often identify psychosocial stress as a factor that exacerbates their symptoms, and many trace the onset of symptoms to a stressful period of life or a discrete traumatic incident. However, the pathophysiological relationship between stress and OCD remains poorly characterized: it is unclear whether trauma or stress is an independent cause of OCD symptoms, a triggering factor that interacts with a preexisting diathesis, or simply a nonspecific factor that can exacerbate OCD along with other aspects of psychiatric symptomatology. Nonetheless, preclinical research has demonstrated that stress has conspicuous effects on corticostriatal and limbic circuitry. Specifically, stress can lead to neuronal atrophy in frontal cortices (particularly the medial prefrontal cortex), the dorsomedial striatum (caudate), and the hippocampus. Stress can also result in neuronal hypertrophy in the dorsolateral striatum (putamen) and amygdala. These neurobiological effects mirror reported neural abnormalities in OCD and may contribute to an imbalance between goal-directed and habitual behavior, an imbalance that is implicated in the pathogenesis and expression of OCD symptomatology. The modulation of corticostriatal and limbic circuits by stress and the resultant imbalance between habit and goal-directed learning and behavior offers a framework for investigating how stress may exacerbate or trigger OCD symptomatology.