The harms associated with substance use represent a public health concern on a global scale, varying according to the substances used, individual characteristics, and contextual factors. This chapter addresses the epidemiology and impacts of substance use in the global context, emphasizing that disorders related to the use of alcohol and other substances affect mental health, quality of life, and well-being, both at micro and macro-social levels. Data from the World Health Organization (WHO) indicate that, in 2016, more than half of the global population aged 15 years or older consumed alcoholic beverages, with a high prevalence of excessive alcohol consumption patterns, such as binge drinking. According to the 2023 World Drug Report by the United Nations Office on Drugs and Crime (UNODC), it is estimated that 36 million people used amphetamines, 22 million used cocaine, and 20 million consumed MDMA, commonly known as “ecstasy”. The excessive use of illicit substances, especially opioids, has been associated with most substance use disorders, with opioids accounting for nearly 70% of deaths related to substance use disorders. Cannabis use among adolescents and young adults also showed high prevalence, with 5.3% of youths aged 15–16 years reporting use in the past year. Health consequences may include impairments in cognitive-socio-emotional development, compromised neurocognitive functions, and long-term health conditions, as well as other psychosocial harms. Prolonged use may be associated with neurobiological alterations, such as changes in synaptic plasticity and inflammatory processes, with effects varying according to genetic, developmental, and sociocultural factors. These variations underscore the importance of a multifactorial understanding of the effects of substance use, without generalizations, taking into account the diversity of neuropsychological profiles and the different contexts in which use occurs.