Obsessive-compulsive disorder (OCD) has emerged as a common but frequently hidden psychiatric disorder which inflicts an intolerable burden on sufferers and demands effective management. For many years, however, OCD was considered treatment resistant and it is only in the past 15 years that effective therapy has become available. The discovery that the symptoms of OCD could be controlled with clomipramine, but not with other tricyclic antidepressants, was a crucial step in the development of effective management of the condition. The ability of clomipramine to treat OCD derives from its potency as an inhibitor of serotonin reuptake. Serotonin reuptake inhibition has become the fundamental requirement for the pharmacological management of OCD. In the past decade selective serotonin reuptake inhibitors (SSRIs) have been shown to be effective in the management of OCD. Meta-analysis comparing the efficacy of clomipramine and SSRIs initially suggest that clomipramine is more effective than SSRIs, but changes in the clinical characteristics of trial populations over time indicate that the meta-analyses may be misleading. In the few direct comparisons of SSRIs and clomipramine, the two treatments have in fact proved equally effective. Attention is now shifting to the impact side effects on efficacy, a particularly important consideration for OCD patients who require long-term medication but are frequently reluctant to take drugs. The limited data available suggest that SSRIs are better tolerated than clomipramine and are therefore more likely to lead to a favourable treatment outcome.