Introduction. Both recurrent depressive disorders and affective bipolar disorders are characterized by the changes in glial tissue. S100B protein is a calcium-binding molecule, mainly secreted by glial cells, which, depending on its concentration, has a trophic or toxic effect on neuronal cells. In the recent years, due to the postulated glial hypothesis of affective disorders and the ideas concerning brain neuroplasticity, there has been a growing interest in S100B protein and its role in affective disorders. Aim and method. The aim of this study was to review the available subject literature from the recent years. This article presents a review of studies from the last years based on the literature available in PubMed/MEDLINE database. Conclusions. In the previous studies conducted in patients with mood disorders it has been shown that the increased S100B protein serum level occurs both in patients with depression and with mania compared to the patients from control group. The studies were mainly conducted on adult population; there are no studies on children and adolescents with bipolar affective disorder so far. The majority of studies indicated the more important association between the increased S100B protein levels and the occurrence of a depressive episode as well as the regulation of S100B protein level during the effective pharmacological treatment, which can be a potential marker of the efficacy of treatment.