This article, part of a comparative research project (WP2) funded by FP7 ALICE RAP, is based upon a review of literature and documents and 18 individual interviews with Italian national stakeholders (SHs) conducted in 2012. The goal was to identify the main shifts in opioid "substitution drug" treatment policies and understand the role played by different SHs during the last 30 years. The study confirms that opioid "substitution drug" treatment is a particularly suitable theme for improving knowledge in the field of SH analysis, even if results show that changes in policies are mainly due to external factors rather than to the action of SHs.