Opioid substitution therapy (OST) is a well-recognised, evidence-based treatment for opioid dependence. Since the early 1990s, Australia has used a community-based general practitioner (GP) model of prescribing, particularly within the state of Victoria, where over 85% of OST prescribing is undertaken by GPs in community settings. Yet the majority of GPs invited to complete the required OST training decline the offer, while of those who complete training, the majority prescribe to few or no patients. This study aimed to determine the reasons for this. Twenty-two in-depth interviews were conducted with Victorian GPs exploring the reasons why the majority declined training, and for trained GPs, why they prescribed to few or no patients in the first 12 months after training. General practitioners who declined to train were predominantly influenced by negative experiences with drug-seeking patients, although other secondary reasons also affected their decision. Some GPs who completed the training were prevented from prescribing by several structural and operational barriers, many of which could be addressed. Fear of deskilling with time became a further impediment. General practitioners who became regular prescribers were highly committed with lengthy general practice experience. Concerns exist about the recruitment process for OST prescriber training, where nearly all GPs decline the offer of training, and the barriers that prevent GPs prescribing after training. Action is needed to address barriers to GP OST training and prescribing, and further research is necessary to ascertain measures required to facilitate long-term prescribing.