BACKGROUND: Allostatic load (AL) relates to the neural and bodily "wear and tear" that emerge in the context of chronic stress. This paper aims to provide clinicians with a comprehensive overview of the role of AL in patophysiology of bipolar disorder (BD) and its practical implications. METHODS: PubMed searches were conducted on English-language articles published from 1970 to June 2011 using the search terms allostatic load, oxidative stress, staging, and bipolar disorder cross-referenced with cognitive impairment, comorbidity, mediators, prevention. RESULTS: Progressive neural and physical dysfunction consequent to mood episodes in BD can be construed as a cumulative state of AL. The concept of AL can help to reconcile cognitive impairment and increased rates of clinical comorbidities that occur over the course of cumulative BD episodes. CONCLUSIONS: Data on transduction of psychosocial stress into the neurobiology of mood episodes converges to the concept of AL. Mood episodes prevention would not only alleviate emotional suffering, but also arrest the cycle of AL, cognitive decline, physical morbidities and, eventually, related mortality. These objectives can be achieved by focusing on effective prophylaxis from the first stages of the disorder, providing mood-stabilizing agents and standardized psychoeducation and, potentially, addressing cognitive deficits by the means of specific medication and neuropsychological interventions.