It is estimated that most substance users are not substance-dependent, yet they misuse alcohol and/or other drugs on a regular basis and are at risk in terms of health and further dependency. Screening, brief intervention, and referral to treatment (SBIRT) is an intervention model that identifies at-risk substance users and then provides them a patient-centered intervention. A review of selected SBIRT initiatives in California revealed a number of positive trends: the involvement of healthcare settings in substance use prevention; an increase in the number of providers trained in substance use screening; greater use of standardized screening tools; indications of reduced substance use by individuals receiving SBIRT; and the establishment of statewide policy initiatives. Despite these positive trends, SBIRT projects continue to face challenges related to leadership support, staff resources, integration into ongoing protocols, screening, client retention, client confidentiality, and data collection. To assist projects to overcome these challenges and to ensure future adoption and sustainability of SBIRT, state and local authorities can benefit from (a) promoting SBIRT among healthcare leaders, (b) identifying and sharing successful SBIRT "models", (c) providing tailored trainings and ongoing technical assistance, (d) educating providers about patient confidentiality and reimbursement laws and regulations, and (e) creating benchmark measures and data collection protocols.