By tailoring the mechanism of action and effects of therapy to the specific nature of each patient’s insomnia and other conditions, clinicians can offer personalized care in an attempt to achieve an improved risk-benefit ratio compared to that of a “one-size-fits-all” treatment strategy. To move toward this personalization and optimization of treatment, clinicians need awareness of the specific effects of interventions and the subpopulations with insomnia who would benefit from each intervention. This report reviews insomnia treatments, focusing on effects associated with mechanism of action.