There is substantial evidence that obsessive-compulsive disorder (OCD) is mediated by specific cortico-striatal- thalamic-cortical (CTSC) circuits. Here we discuss very recent publications that address the following questions: How does damage to CSTC circuitry come about?; What are the neurochemical systems involved in mediating this circuitry?; and What are the implications of such damage for understanding the pathogenesis and management of OCD? A cognitive-affective neuroscience perspective is helpful in advancing our understanding of the role of these circuits in OCD and the dysfunctional procedural strategies that appear to characterize this disorder. Furthermore, this model is becoming integrated with a range of data including brain imaging, genetic, immunologic, and neurochemical findings.