The discovery of lithium in 1946 led to a revolution in the management of bipolar disorder as well as other psychiatric conditions. Since that time and especially in the past 20 years, treatment options for bipolar disorder have progressively advanced such that a modern practitioner has a number of evidence-based options to manage the illness. However, the evidence is strongest in adults for acute mania and weakens in other mood states and in youth. Nonetheless, based on the available evidence, this chapter provides recommendations for first-, second-, and third-line pharmacological treatments for bipolar illness to guide clinicians. Additionally, specific considerations for the various medications are reviewed. Suggestions are provided for both adults and youth.