There is an enduring and prevailing disparity between the clinical prevalence of alcohol, tobacco and other drug-related problems and the frequency that nurses recognise and intervene in these common problems. The extant nursing literature has long determined an urgent need for further investigation into why nurses do not respond to patients with ATOD-related problems in the consistent and effective manner that the prevalence of these costly health problems require, or in a manner that reflects the opportunities that nurses have to offer brief and timely intervention. This thesis reports and discusses the investigation of factors that determine identification, assessment and interventions of patients with alcohol, tobacco and other drug-related problems by a randomly selected sample of Registered Nurses [n=1281] in practice in New South Wales, Australia. Of particular interest was the relationship between nurses' ATOD knowledge, therapeutic attitudes and clinical activity. Multiple quantitative and qualitative methods were used, firstly to systematically investigate factors within the nurse and their clinical setting that might predict desired clinical behaviour towards addressing ATOD-related problems, and secondly, to analyse and describe nurses' self-reported perceptions, views and experiences of the issue and what aids or impedes it. The research instrument - a 72 item self-completed questionnaire was developed and refined within a process of three (3) pilot studies and test-retest method. A multiple regression model was developed to establish the predictors of key clinical behaviours. Thematic coding was used to analyse the perceptions of these nurses as to the factors that affect their ability to intervene with patients who have ATODrelated problems. Convergent and divergent concerns between quantitative and qualitative findings became apparent. Thematic analysis of open-ended responses demonstrated that nurses report a complex of factors that affect their ability and capacity to intervene with patients who have ATOD-related problems. Among these are factors located within nurses themselves, within their patient(s), within their workplace, within other health professionals and within the broader social/cultural context. The latter part of the thesis systematically considers the relationships between the quantitative and qualitative findings within this large sample of registered nurses. From this comprehensive level of analysis, workforce implications for ATOD education, training and organisational support for nurses, the most numerous group of health care workers, have been readily identified. The major empirical finding of this investigation is that there is a significant difference between positive attitudinal sets and motivation of practicing registered nurses to perform desired ATOD-related clinical activities, and the lower reported frequency at which this occurs. The qualitative findings are highly convergent with the empirical ones. It is the nurse's self-identified lack of knowledge, skills, experience and confidence that is now reported as having the greatest effect on their ability to assess, identify and offer brief and timely intervention for patients with ATOD-related problems, rather than any prevailing beliefs and attitudes that these patients were not worthy of their care, or outside the legitimate framework of their nursing role.