While controlled trials with SRIs have demonstrated a selective efficacy in obsessive-compulsive disorder (OCD), up to 40-60% of patients do not have a satisfactory outcome. Non-response to treatment in OCD is associated with serious social disability. There are a large number of non-responsive patients, and they are difficult to cluster due to ambiguities in diagnostic criteria, possibility of subtypes and a high rate of comorbidity. Moreover, the findings of current studies of "so-called" non-responsive cases are currently non-generalizable because of the lack of an operational definition of non-response. The result has been that a cumulative body of data on a reasonably homogeneous sample of non-responders has not been developed. The aims of the research in this area are to clarify some of the obstacles in defining stages of response and levels of non-response and, through a comprehensive analysis, to propose a systematic nosology for this rather common condition. Better characterization of which patients respond and do not respond to various treatments will enable more accurate clustering of patients, and help facilitate multisite data collection for future research trials. The authors reviewed also the more recent therapeutic pharmacological and psychological lines for the treatment of refractoriness in OCD.