Historically, the response of the Vietnamese government to illicit drug use and HIV has been slow and ineffective. However, 2006 saw the government formally endorse harm reduction interventions. This paper examines the views of senior key informants inside Vietnam on the development of an advocacy strategy for harm reduction. Twenty-nine informants were interviewed across public health, public security, social affairs and other international bodies, including United Nations agencies and international non-governmental organisations. Challenges and barriers identified for harm reduction progress included: promoting a nationwide understanding and acceptance of harm reduction and the HIV Law; lack of skilled resources, training programmes and technical capacity; poor coverage of interventions; and gaps in the sharing of information. There is currently a government-led shift in Vietnam in the response to the prevailing HIV epidemic among drug users, but ensuring that the HIV Law can operate unhindered is critical. The implementation of a response to illicit drug use and HIV remains an enormous challenge. With appropriate technical education and training, ongoing advocacy, and a cohesive, coordinated multi-sectoral effort, the capacity of the government and community to adopt, support and promote measures to reduce HIV and other drug-related harms will be markedly strengthened.