This report was prepared for the Substance Abuse and Mental Health Services Administration (SAMHSA) to disseminate information on telehealth evidence-based practices and service delivery models to prevent substance misuse and help with substance use disorders (SUDs), serious mental illness (SMI) and serious emotional disturbances (SEDs). This guide reviews literature and research findings related to telehealth modalities, examines emerging and best practices, discusses gaps in knowledge, and identifies challenges and strategies for implementation.