Ministries of Finance (MoF) cannot ignore the major challenge to development posed by HIV/AIDS. To tackle the epidemic a new comprehensive and consistent approach is required: HIV/AIDS must be mainstreamed. This paper investigates the instruments MoF do, can, and should employ in order to be proactive and effective in mainstreaming HIV/AIDS through supporting the implementation of the ‘three ones’, promoted by UNAIDS and other partners – One strategic framework, One Authority, and One Monitoring and Evaluation (M&E) System.