Bipolar disorder (BD) has been a particularly challenging illness for the development of adequate animal models for neurobiological studies. These difficulties are largely related to the peculiar clinical characteristics of this illness, with an intriguing alternation of mania, depression, euthymia, and mixed states. The etiology and brain mechanisms involved in this several mental illness remain unknown. Preclinical studies with animal models of mania or depression have been developed to evaluate the potential efficacy of new psychotropic drugs and generate information concerning the biochemical effects of these drugs on specific targets. These models try to mimic the behavioral components of mania and depression in human subjects and examine the pharmacological responses and mechanisms of action of potentially new therapeutic agents. The main limitation is that there is currently no model that would mimic mood cyclicity, which is a hallmark feature of BD. Thus, these models do not represent valid paradigms for the study of this illness, because they do not address key questions regarding cyclicity. In this review, we propose that new genetics approaches involving potential animal models of BD are a promising new area for further development.