Across all care environments, pharmacists play an essential role in the care of people who use and misuse psychoactive substances, including those diagnosed with substance use disorders. To optimize, sustain, and expand these independent and collaborative roles, the Association for Multidisciplinary Education and Research in Substance Use and Addiction (AMERSA) has developed core competencies for pharmacists to address substance use in the 21st century. Key concepts, skills, and attitudes are outlined, with links to entrustable professional activities to assist with integration into a variety of ideally interdisciplinary curricular activities.