Bipolar disorder (BD), also known as manic-depressive illness, is a serious mental illness that causes unusual shifts in mood, energy, activity levels, and the inability to carry out day-to-day tasks. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) recognizes a spectrum of bipolar diagnoses that differ in duration of bipolar episodes/periods and impairment: bipolar I disorder (BD-I), dipolar II disorder (BD-II), BD otherwise specified, and BD unspecified. Prevalence studies estimate about 1 percent of the population for BD-I, another 1 percent for BD-II, and up to 5 percent for the full spectrum of BD diagnoses, with relatively similar prevalence in men and women and across cultural and ethnic groups. BD represents a significant individual and societal burden. Recurrent episodes of mania and depression can cause serious impairments in functioning, such as erratic work performance, increased divorce rates, and psychosocial morbidity. People with bipolar disorder account for between 3 and 14 percent of all suicides, and about 25 percent of bipolar disorder patients will attempt suicide. Further adding to the individual illness burden, 92 percent of individuals with BD experience another co-occurring psychiatric illness during their lifetime. Of all psychiatric conditions, BD is the most likely to co-occur with alcohol or drug abuse disorders. Treatment of BD generally begins with the goal of bringing a patient with mania or depression to symptomatic recovery and stable mood. Once the individual is stable, the goal progresses to reducing subthreshold symptoms and preventing relapse into full-blown episodes of mania and depression. Drug treatments have several purposes. Some drugs aim to reduce symptoms associated with acute manic or mixed mania/depression episodes, some aim to reduce acute depression symptoms, and others aim to reduce acute symptoms, maintain relatively symptom-free periods, and prevent relapsing to acute episodes. Given the chronic, relapsing/remitting course of bipolar disorder and the need for maintenance treatment in many patients, drugs begun for an acute mood episode (including mania) are often carried forward into maintenance therapy. Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for practice, systematic reviews can help clarify whether assertions about the value of the intervention are based on strong evidence from clinical studies. The purpose of this review is to assess the effectiveness of drug and nondrug therapies for treating acute mania or depression symptoms and preventing relapse in adults with bipolar disorder (BD) diagnoses, including bipolar I disorder (BD-I), bipolar II disorder (BD-II), and other types. Key messages addressed are: -Acute mania treatment: Lithium, asenapine, cariprazine, olanzapine, quetiapine, risperidone, and ziprasidone may modestly improve acute mania symptoms in adults with BD-I. Participants on atypical antipsychotics, except for quetiapine, reported more extrapyramidal symptoms, and those on olanzapine reported more weight gain, compared with placebo; -Maintenance treatment: Lithium may prevent relapse into acute episodes in adults with BD-I; -Depression treatment: Evidence was insufficient for drug treatments for depressive episodes in adults with BD-I and BD-II; -For adults with any BD type, cognitive behavioral therapy may be no better than other psychotherapies for improving acute bipolar symptoms and systematic/collaborative care may be no better than other behavioral therapies for preventing relapse of any acute symptoms; -Stronger conclusions were prevented by high rates of participants dropping out.