Misuse of psycho-active substances is frequent in primary care and concerns patients of all ages and conditions. Physicians should screen for use of such substances, especially in the case of tobacco dependence and/or clinical symptoms. Independently from the substance used (or from the behaviour), screening can be performed through clinical interviewing, focusing on the frequency and the quantity of the substance used, loss of control and its consequences, or through screening tools. Questionnaires (ASSIST; AUDIT; FACE) allow both screening and evaluation of the severity of misuse, guiding appropriate advice, treatment or referral to specialist. Motivational interviewing is the best option to discuss and induce behavioural changes.