Treatment resistant patients with Obsessive-Compulsive Disorder (OCD) are those who undergo adequate trials of first-line therapies without a satisfactory response. Two major options are available for those patients: 1) augmentation with cognitive-behavioral therapy (CBT) or pharmacotherapy, and 2) switch to another compound or to another formulation. The first approach is to augment the serotonin reuptake inhibitor (SRI) with CBT or with another drug. In the first case preliminary data indicate that exposure and response prevention is effective. Pharmacological augmentation has been tried with several drugs; the effectiveness of antipsychotic (first and second generation) augmentation is well documented and subjects with comorbid tic may be particularly responsive to haloperidol. A second, although less established, augmentation strategy consists in adding another SRI. Other drugs like pindolol and morphine have shown efficacy in few controlled studies. The second approach, less studied, is switching from a serotonergic compound to another one (generally from a selective serotonin reuptake inhibitor to clomipramine or vice-versa), or to venlafaxine or mirtazapine. Finally, patients that failed to respond to oral clomipramine might benefit from switching to the IV clomipramine. The augmentation strategy should be considered in case of partial response while the switch strategy in absence of any minimal improvement.