This chapter reviews the empirical literature on different definitions of mixed state (MS) focusing on their clinical validity. A large literature is available indicating that the Diagnostic and Statistical Manual, 4th edn. (DSM-IV) threshold for syndromal depression during mania is too restrictive, and suggesting that few depressive symptoms would suffice in validating the clinical diagnosis of mixed mania. Depressive-MS patients can be distinguished from non-mixed bipolar depressives by the fact that they have fewer episodes of longer duration, and frequently begin their illness with a mixed episode. Among the (hypo) manic symptoms reported in depressive MS, flight of ideas, racing thoughts, and distractibility belong to the same dimension of psychic excitement. Affective instability, fluctuation, lability, irritability, and diurnal variation emerge as the core phenomenologic features of mixed bipolar states; perplexity, psychotic experiences, and grossly disorganized behavior seem to arise from this protracted instability.