Recent data show that biomarkers differ in early and late-stage bipolar disorder (BD). Here we propose a model of staging for bipolar disorder that emphasizes the potential use of biomarkers for differentiating early and late-stage BD patients in the inter-episodic period. The proposed model includes a Latent phase: patients at "ultra-high-risk" for developing BD, characterized by a family history of BD, temperament traits, mood, and anxiety symptoms as well as genetic vulnerability for developing the disorder; Stage I: patients who return to their baseline level of functioning when mood episodes resolve; Stage II: biomarkers and functioning impairment are related to comorbidities or rapid-cycling presentations; Stage III: persistent cognitive and functioning impairment in the inter-episode period as well as changes in biomarkers; and Stage IV: same findings as in Stage III associated with extreme cognitive and functioning impairment, to the point that patients are unable to live autonomously. Empirical testing will determine the ability of the present model to inform patients and clinicians about both prognosis and response to treatment.