Managing bipolar mixed states should start by establishing a diagnosis, assessing for comorbidities, and clarifying targets for therapy. Differentiating between unipolar and bipolar disorder is important because these conditions have dissimilar efficacious pharmacotherapeutic options. To treat mixed states, atypical antipsychotics or divalproex have been shown to be effective, and antidepressants should generally be avoided. Because of the complexity of mixed episodes, monotherapy may be insufficient and patients may require combination treatment. As more medications become available in the treatment of bipolar disorder, algorithms can help clinicians make the appropriate treatment choices by offering recommendations for sequencing agents.