The purpose of this article is to introduce the reader to an updated evidence-based drug treatment algorithm to be employed in patients with obsessive-compulsive disorder (OCD). Relevant studies were identified through a comprehensive review and classified according to the type of patients enrolled, the quality of the study design and the invasiveness, availability and complexity of the therapeutic approach. When ineffective, therapeutic trials with first-line strategies (such as the selective serotonin re-uptake inhibitors [SSRIs] and venlafaxine) should be followed by treatment approaches such as clomipramine, augmentation with antipsychotics or pindolol, SSRI megadoses or cognitive behavioral therapy. These therapeutic strategies are expected to help most patients with OCD. Additional approaches include intravenous clomipramine, oral morphine, 'heroic drug strategies', deep brain stimulation and functional neurosurgery. Independent studies are urgently needed to help identify the most promising drug treatment sequences for OCD.