Addiction is a chronic-relapsing brain disorder characterized by cognitive, behavioral, and physiological symptoms including compulsion to take the drug, loss of control over use, and persistent consumption despite substance-related problems. Individual susceptibility is influenced by genetic, psychological, and environmental factors; age of first exposure; substance characteristics; and pattern of use. Substances of abuse act on several brain’s systems leading to persistent changes, which can trigger relapse even after prolonged abstinence. Addiction is a major public health concern. About 35.6 million people worldwide suffer from substance use disorders (SUDs), whose prevalence is expected to continue to grow. SUDs are associated with psychiatric conditions, adverse health consequences, and social disadvantage. Despite their high prevalence and their impact in terms of mortality, morbidity, and societal costs, health-care providers report inadequate preparedness in recognizing and supporting patients with SUDs. Awareness of risk factors, knowledge of the underlying neurobiological mechanisms and identification of early signs make it possible to implement prevention and treatment strategies for SUDs. Therefore, this chapter aims to discuss the identification, management, and treatment of substance-related disorders, providing health-care professionals with fundamental tools to face one of the most challenging public health threats to our society.