Bipolar disorder (BD) is a chronic pathology with a worldwide prevalence of 2.4% in its classic presentations. Studies show that the depressive, mania/hypomania crises are neurotoxic and cognitive impairment is present both in the acute phases as well as in euthymia. However, bipolar type I patients have more cognitive changes than type II patients, most likely due to greater toxicity of manic episodes, with greater release of inflammatory cytokines, reduction of brain-derived neurotrophic factor (BDNF), higher oxidative stress and, consequently, loss of neuroprotective mechanisms. In this sense, more than the time of disease duration, the number of manic episodes seems to determine the exacerbation of cognitive decline, mainly in patients presenting psychotic symptoms.