The World Health Organization has determined that obsessive-compulsive disorder (OCD) is the 10th leading medical cause of disability across the globe. Unfortunately, a substantial proportion of patients with OCD fail to respond to medication trials. In the pivotal double-blind, placebo-controlled trials that established the efficacy of clomipramine and the selective serotonin reuptake inhibitors (SSRIs), 40% to 60% of patients were nonresponders to a given drug. Moreover, patients who do not respond to their first medication trial may be less likely than treatment-naive patients to respond to subsequent trials. For example, only 33% of patients participating in double-blind trials who had failed trials of one or more serotonin reuptake inhibitors (SRIs) benefited from a subsequent trial of sertra-line, compared with 53% of those who were treatment naive (Rasmussen, Baer, Eisen, and Shera, unpublished data, 15th Annual Meeting, American Psychiatric Association, May 17-22, 1997).At the Fourth International Obsessive-Compulsive Disorder Conference, held in February 2000 in St. Thomas, US Virgin Islands, an afternoon panel was devoted to considering issues and strategies related to treatment-refractory OCD. The panel presentations were divided into three groups: time to response and outcome after long-term followup; pharmacologic strategies for nonresponders; and new data concerning nonpharmacologic interventions.