Functional imaging studies indicate involvement of the cortico-striatal-thalamic-cortical circuit in Obsessive-compulsive disorder (OCD) pathophysiology. This chapter reviews positron emission tomography (PET) and single photon emission computed tomography (SPECT) binding studies on serotonin and dopamine, and all available 1H magnetic resonance spectroscopy (1H MRS) research into glutamate levels in OCD. It combines these findings into a pathophysiological model for dysfunctional neurotransmission in OCD. Eight studies have investigated serotonergic neurotransmission in OCD, by comparing the availability of serotonin transporter (SERT) or 5-HT2a receptors between patients and healthy controls. Five studies used 1H MRS to estimate brain levels of glutamate in OCD patients and healthy controls, including one study that performed measures before and after serotonin reuptake inhibitors (SRI) treatment. Results from SPECT and PET binding studies suggest that OCD is related to decreased presynaptic SERT availability in thalamic and midbrain-pons regions, along with increased post-synaptic 5-HT2a receptor availability in cortical areas.