In the last 20 years, functional magnetic resonance imaging (fMRI) has been extensively used to investigate system-level abnormalities in the brain of patients with obsessive-compulsive disorder (OCD). In this chapter, we start by reviewing the studies assessing regional brain differences between patients with OCD and healthy controls in task-based fMRI. Specifically, we review studies on executive functioning and emotional processing, protocols in which these patients have been described to show alterations at the behavioral level, as well as research using symptom provocation protocols. Next, we review studies on brain connectivity alterations, focusing on resting-state studies evaluating disruptions in fronto-subcortical functional connectivity and in cortical networks. Likewise, we also review research on effective connectivity, which, different from functional connectivity, allows for ascertaining the directionality of inter-regional connectivity alterations. We conclude by reviewing the most significant findings on a topic of translational impact, such as the use of different fMRI measurements to predict response across a variety of treatment approaches. Overall, results suggest that there exists a pattern of regions, involving, but not limited to, different nodes of the cortico-striatal-thalamo-cortical circuits, showing robust evidence of functional alteration across studies, although the nature of the alterations critically depends on the specific tasks and their particular demands. Moreover, such findings have been, to date, poorly translated into clinical practice. It is suggested that this may be partially accounted for by the difficulty to integrate into a common framework results obtained under a wide variety of analysis approaches.