Poor adherence to medication can have devastating consequences for patients with serious mental illness. The literature review and recommendations in this article are reprinted from The Expert Consensus Guideline Series: Adherence Problems in Patients with Serious and Persistent Mental Illness, published in 2009. The expert consensus survey (39 questions, 521 options) on adherence problems in schizophrenia and bipolar disorder was completed by 41 experts in 2008. This article first reviews the literature on interventions aimed at improving adherence. It then presents the experts' recommendations for targeting factors that can contribute to nonadherence and relates them to the literature. The following psychosocial/programmatic and pharmacologic interventions were rated first line for specific problems that can lead to nonadherence: ongoing symptom/ side-effect monitoring for persistent symptoms or side effects; services targeting logistic problems; medication monitoring/environmental supports (e.g., Cognitive Adaptation Training, assertive community treatment) for lack of routines or cognitive deficits; and adjusting the dose or switching to a different oral antipsychotic for persistent side effects (also high second-line for persistent symptoms). Among pharmacologic interventions, the experts gave high second-line ratings to switching to a long-acting antipsychotic when lack of insight, substance use, persistent symptoms, logistic problems, lack of routines, or lack of family/ social support interfere with adherence and to simplifying the treatment regimen when logistic problems, lack of routines, cognitive deficits, or lack of family/social support interfere with adherence. Psychosocial/programmatic interventions that received high second-line ratings in a number of situations included medication monitoring/environmental supports, patient psychoeducation, more frequent and/or longer visits if possible, cognitive behavioral therapy (CBT), family-focused therapy, and services targeting logistic problems. It is important to identify specific factors that may be contributing to a patient's adherence problems in order to customize interventions and to consider using a multifaceted approach since multiple problems may be involved.