Lithium, one of the oldest and most studied psychiatric medications, remains the first-line option in the treatment of bipolar disorder. It is effective, especially in the treatment of mania and for the prevention of manic and depressive recurrences. It can also be helpful in the treatment of depression, especially as an augmenting agent, and for reducing the risk of suicide. More recently, it has attracted attention for its neuroprotective effects. In this chapter, we review the pharmacology of lithium, its psychiatric indications, and address the most relevant and practical aspects of lithium treatment.