Bipolar patients with early-onset, comorbid substance abuse, rapid cycling, and mixed episodes are difficult to treat and frequently require rational polypharmacy. When polypharmacy is unsuccessful, the clinician must consider the off-label use of newer psychotropics. Levetiracetam is a novel anticonvulsant with antikindling, inhibitory, and neuroprotective properties that is effective in an animal model of mania. This case report describes a patient with treatment-resistant rapid cycling bipolar disorder who failed 15 psychotropics, individually or in various combinations (maximum of 6), but ultimately responded to levetiracetam monotherapy and remained without bipolar features during 1 year of maintenance treatment, excluding 1 week during which the patient was medicine noncompliant. Further, methylphenidate used to treat comorbid attention deficit disorder did not precipitate manic features. Levetiracetam should be further studied for its potential use in the treatment of bipolar disorders.