Harmful substances and behaviours include alcohol, drugs, smoking, gambling, harmful technology use, and risky sexual practices, with a spectrum of harm from minimal to severe. Stigma and discrimination compound the harmful effects of these substances and behaviours. The biopsychosocial model has been historically used to understand, assess, and intervene in problems with such substances and behaviours. Harmful use of substances and behaviours is a growing problem and contributes significantly to the global burden of disease. The rise of technology-driven behaviours, such as gaming and social media use, can lead to addictive or compulsive patterns. Alcohol is a leading risk factor for disease and death, with no safe level of consumption recommended by the World Health Organization. Misuse of illicit and prescription drugs is rising globally, with opioids contributing to the most significant drug-related harm. Tobacco use remains a major modifiable risk factor for disease and mortality. Problem gambling has a high suicide rate and is often accompanied by financial problems. Definitions of problematic use of gaming and other technologies are challenging, with varying cultural and generational views on acceptable levels.