BACKGROUND The quest toward more effective treatments for bipolar disorder (BD) solicits novel drugs and further research on the underpinning neurobiology. The present review aims to critically appraise the existing evidence about the pharmacological treatment of BD toward the development of novel treatment avenues. METHODS The present review appraises animal and human studies concerning both the currently available psychotropic drugs, and the general medicine drugs which may represent a path toward the development of novel drugs for BD. PubMed and Scopus were last accessed on February 20th, 2021 for records indexed upon inception relevant to the pharmacological treatment of BD. Immune-modulating agents, anti-inflammatory agents, and glutamate antagonists represent the most intriguing potential targets for the development of new drugs for BD, thus receiving critical appraisal in the present text. CONCLUSIONS Regardless of the neurobiological pathways worthy of investigation toward the development of experimental drugs for BD, several unmet needs need to be addressed first. In particular, several biomarkers are altered in BD. However, it is the opinion herein expressed by the authors that it remains uncertain what comes first, that is peripheral changes or the disease.