Current diagnostic systems (DSM-IV-TR and ICD-10) do not include depressive mixed state (DMS) as a separate category. However, both historical descriptions and data from recent research clearly indicate that cooccurrence of (hypo)maniacal and depressive symptoms is standard in clinical picture of affective disorders. Most frequently employed criterion for DMS is the presence of at least three symptoms of (hypo)mania for 7 days during a major depressive episode. Not only formal diagnostic criteria for DMS are lacking but also psychometric assessment tools (for example the Hamilton Depression Scale or the MADRS) were designed around the features of “classical” depression. The other obstacles to recognize DMS could be lack of insight into the (hypo)maniacal symptoms in patients and cognitive dysfunctions present during an episode. On the other hand, newly created instrument, the Bipolar Depression Rating Scale, may assist clinical evaluation of DMS. Despite predominating depressive symptomatology, the principles of treatment of DMS suggest avoidance of antidepressant monotherapy in favor of mood stabilizers’ administration. Actually DMS may emerge as a complication of antidepressant monotherapy in some bipolar patients or may be induced with interferon-alpha treatment in some chronic hepatitis C patients. Important consequences of both spontaneous and drug-induced DMS could be the roughening of affective symptomatology, resistance to antidepressants and the increase of suicidality. Thorough appraisal of symptoms seen in patients with affective disorders for indicators of DMS could have critical consequences for functional outcomes.