Replicated evidence indicates that bipolar disorder is associated with alterations in molecular, cellular, and neuro systems that involve disparate metabolic and inflammatory pathways. Conventional treatments for bipolar disorder have largely been identified serendipitously rather than based on an a priori disease model. Consensus exists that available treatments for bipolar disorder are neither disease modifying nor targeting critical effector systems implicated in this disorder. This presentation will provide a rationale for exploring drug development opportunities for critical metabolic systems including glucagon-like-peptide and insulin systems as well as critical inflammatory pathways. Novel proof of concept data will be presented for several novel pharmacological approaches, e.g. insulin, minocycline, and infliximab.