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Background: Psychoactive substances have toxic effects resulting different cardiovascular and non-cardiovascular organ damage. Through a variety of mechanisms, they can trigger the onset of various forms of cardiovascular disease: acute or chronic, transient or permanent, subclinical or symptomatic. Hence, a thorough knowledge of the patient's drug habits is essential for a more complete clinical-etiopathogenetic diagnosis and consequent therapeutic, preventive, and rehabilitative management. Summary: The prime reason for taking a psychoactive substance use history in the cardiovascular context is to identify those people who use substances (whether habitual or occasional users, symptomatic or not) and adequately assess their overall cardiovascular risk profile in terms of "user status" and type of substance(s) used. A psychoactive substance history could also alert the physician to suspect, and eventually diagnose, cardiovascular disease related to the intake of psychoactive substances, so optimizing the medical management of users. This anamnesis could finally assess the likelihood of patients persisting in the habit as a user or relapse, while maintaining high their cardiovascular risk profile. Taking such a history should be mandatory when a causal connection is suspected between intake of psychoactive substances and the observed symptoms or pathology, regardless of whether the individual is a declared user or not. Key Messages: The purpose of this article was to provide practical information on when, how, and why to perform a psychoactive substance use history. [ABSTRACT FROM AUTHOR]