Bipolar disorder (BD) is one of the complex syndromes in psychiatry. At present, the pathophysiology of BD is not well understood. Furthermore, drugs used to treat BD as monotherapy have an efficacy either in manic or depressive pole, and classified in different groups (e.g. antipsychotics, anticonvulsants). Therefore, many hypotheses have been proposed for the molecular mechanism of these drugs in BD. This article focuses on 3 hypotheses which include 1) the GSK-3 inhibition hypothesis insists that inhibition of GSK-3 results in attenuation or prevention of apoptosis, 2) the arachidonic acid cascade hypothesis asserts that downregulating brain arachidonic acid metabolism alleviate BD symptoms, particularly bipolar mania, and 3) the myo-inositol depletion hypothesis affirms that lithium exerts its mood stabilizing effect by decreasing inositol concentrations. In addition, mechanisms of quetiapine and lamotrigine on cell surface receptors and membrane proteins (e.g. transporters, ion channels) which may involve bipolar depression are mentioned. However, further studies may be required for more evidences of disease mechanisms and drug targets in BD.