Purpose of Review <p>Lithium is considered to have substantial benefits and harms, which constitutes a complex clinical challenge. This article aims to cover five putative strategies to maximise the benefits of lithium therapy while concurrently minimising its harms.</p> Recent Findings <p>The strategies range in terms of their evidence base. Some are supported by long-standing evidence, namely the management of some common and/or severe adverse effects. For others, we are seeing emerging research focus, particularly in the use of lithium in ‘sub-therapeutic’ doses. In considering gradual titration and variable dosing, as well as innovation to enhance the monitoring of lithium, there is limited evidence which is reviewed.</p> Summary <p>We conclude that optimising lithium therapy is not straightforward and clearly individual patient characteristics must be thoroughly prioritised. However, a general rule for optimising can be to maintain lithium at its lowest therapeutic level for an individual patient, with close monitoring of levels and adverse effects as well as careful titration where clinically indicated.&#xa0;</p>