There is evidence that bipolar patients may present reduced life expectancy as well as accelerated aging. Medical comorbidity is also frequent among patients with bipolar disorder and this is more apparent in late stages of the disorder. The model of allostatic load, that emphasizes the "wear and tear" process related to chronic stress may be a way to conceive the burden imposed by mood changes in the brain and in the whole body. Mediators of allostasis include certain neurotransmitters, oxidative stress, hormones related to stress, inflammation and neurotrophins. All these elements have been shown to be changed in bipolar patients and may be considered a platform of new candidates for intervention in bipolar patients.