Despite the numerous advances in psychiatry such as neuroimaging techniques, structured interviews, and comprehensive diagnostic protocols, all too frequently a patient's symptomatology does not fit neatly into a recognized diagnostic category. Given the increasing popularity of treatment guidelines, purportedly predicated on hard science, clinical uncertainty becomes increasingly problematic, precisely because the guidelines are aimed at specific and discrete psychopathological categories. On the one hand, clinical reality is complex, contradictory, and most certainly contested. On the other, medical training and professional demands require that the psychiatrist demonstrate certainty, be it to patients, colleagues, health insurance providers, other third parties, and perhaps most controversially, to themselves. Faced with clinical uncertainty, the clinician may find herself or himself in a difficult situation: recognition of the uncertainty is regarded as an indication of poor professional performance, whereas assertion of a diagnosis or plan of treatment runs a very real possibility of contravening the beneficence principle. Clinical uncertainty is all the more pronounced in the face of certain mental disorders, cultural, age, and gender difference, and training model. This paper will examine some of the key factors related to clinical uncertainty and how it relates to clinical practice. It will be suggested that clinical uncertainty itself represents an important source of diagnostic information and rather than be ignored should in fact be incorporated into the diagnostic and treatment process.