Substance use seems to be associated with increased prevalence levels of violent behaviour in both general population and psychiatric patients, with 'dual diagnosis' clients showing high rates of risky and criminal behaviour and worse therapy compliance. Cases of drug-related aggressiveness mostly involve a number of molecules, e.g. ethanol, stimulants, cannabinoids, opiates, benzodiazepines, synthetic cannabinoids and synthetic cathinones. Consumers of the virtually few hundreds, and up to a few thousands substances currently available may present to the emergency departments without providing information about the substances(s) ingested and it is likely that standard drug tests will show negative results. An appropriate treatment/management plan to cope with the related acute behavioural and psychopathological disturbances is here discussed. Because of the complex behavioural and medical toxicity issues associated with drug intake, raising awareness and education of health care professionals on drugs' health harms, interventions, harm reduction techniques, and referral pathways are here deemed of particular relevance.