This paper explores some of the key issues and challenges of government HIV/AIDS prevention and treatment programme in Nepal. Providing HIV/AIDS prevention and treatment services in Nepal is associated with a number of issues and challenges which are shaped mostly on cultural and managerial issues from grass root to policy level. Numerous efforts have been done and going on by Nepal government and non-government organization but still HIV prevention and treatment service is not able to reach all the most at risk populations because cultural issues and managerial issues are obstructing the services. The existing socio-cultural frameworks of Nepal do not provide an environment for any safe disclosure for person who is HIV infected. Thus, there is an urgent need to address those issues and challenges and strengthen the whole spectrums of health systems through collaborative approach to achieve the millennium development goals. It will be the purpose of this paper to contribute to the policy makers by exploring the pertinent issues and challenges in the HIV/AIDS programme.