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 disroder have largely been identified serendipitiously rather than based on an apriori disease model. consensus exists that available treatments for bipolar disroder are neither disease modifying nor targeting critical effector systems implicated in this disorder. This presentation will provide a rationale for exploring drug development opportunites 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.