Up to sixty percent of people admitted to acute mental health services in Australia present with a clinically significant co-occurring drug and/or alcohol problem. These individuals experience poorer health outcomes when compared to the general population and to those people who have a mental illness but have no co-morbid alcohol and drug problems. Anecdotal evidence also suggests that many nurses working in the area do not have the knowledge and skills and confidence to work effectively with this patient population. Drug and alcohol assessment tools, considered the gold standard, generally assess only one substance at a time or provide little specific information on the particular substance of use or abuse. An amended version of the World Health Organisation, (WHO) Alcohol Smoking and Substance Involvement Screening Test Version 3 (ASSIST V3.0) and associated brief interventions was implemented following an in-vivo education program at an acute mental health inpatient unit in Western Australia. This before and after intervention’ study utilised a self-rating questionnaire and a knowledge quiz to assess nurses’ knowledge of drug and alcohol issues as well as their level of confidence to work with people who have a mental illness and co-occurring drug and alcohol problems. Translation of acquired knowledge into patient care was also evaluated through a review of patient medical records. Significant improvement in nurses’ knowledge was reported along with increased clinical confidence and skills to identify, assess, and manage this group of patients and to provide them with information and referral to appropriate agencies in the community.