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Nurses form a core component of many health care systems so their role in responding to problems related to psychoactive substance use is crucial. They are often under-utilized, mainly because of anxieties concerning role adequacy, legitimacy, lack of support and failure to implement interventions in a variety of settings. Nurses have unique opportunities through interactions they have with young people, families and significant others. Training and career preparation should encompass development of innovative strategies, taking a leading role in management of substance use patients, involvement in the treatment of the homeless mentally ill, HIV-infected individuals and persons with dual disorders of mental health and substance use. Future directions should focus on developing skills for critical thinking, preventive and therapeutic interventions, clinical judgement, effective organizational capacity and team work. Barriers such as scope of practice, authority, ethical and legal issues surrounding health care for substance use need to be addressed.