Despite the high burden of bipolar disorder and the noticeable progress in its treatment, the disorder still goes frequently misdiagnosed, unrecognized, or not optimally treated. To date, no medication has been specifically developed on the basis of a precise understanding of the pathophysiology of the disorder, or based on the unique characteristics of several subtypes of bipolar disorder or on the medication mechanism of action. Lithium remains on of the gold standard treatments for bipolar disorder. Its mood-stabilizing properties are thought to occur via specific cellular signaling pathways, such as inhibition of glycogen synthase kinase 3, which is considered to regulate cellular apoptosis. Divalproex, carbamazepine and several atypical antipsychotics are also approved for bipolar disease Evidence also suggests that antipsychotics show the ability to treat and prevent mania and/or depression but are often burdened by side effects such as sedation, hortostatic hypotension and weight gain. Hence, while it is clear that there still are several unmet needs especially for what pertains tolerability, efficacy for specific subtypes, and predictability. Novel and more effective treatments are needed and researchers are currently engaging in targeted drug development for bipolar illness, aimed at improving pharmacological strategies with marked and sustained effects. A variety of newer medications are being tested. Some of these drugs target pathways that are similar to those targeted by lithium, while others focus on newer targets, such as opiate receptor and N-methyl-D-aspartate (NMDA) receptors. Newer and older treatment strategies for bipolar disorder will be presented and critically reviewed.