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In bipolar disorder illness progression has been associated with a higher number of mood episodes and hospitalizations, poorer response to treatment, and more severe cognitive and functional impairment. This supports the notion of the use of staging models in this illness. The value of staging models has long been recognized in many medical and malignant conditions. Staging models rely on the fact that different interventions may suit different stages of the disorder, and that better outcomes can be obtained if interventions are implemented earlier in the course of illness. Thus, treatment planning would benefit from the assessment of cognition, functioning and comorbidities. Staging may offer a means to refine treatment options, and most importantly, to establish a more precise diagnosis. Moreover, staging could have utility as course specifier and may guide treatment planning and better information to patients and their family members of what could be expected in terms of prognosis. The present study reviews the clinical and biological basis of the concept of illness progression in bipolar disorder.