One of the main problems in Southern Africa in relation to HIV/AIDS is food insecurity. The vicious relation between malnutrition, HIV infection and AIDS impact drives individuals, households and communities in a downwards spiral of impoverishment. Although scientists and development practitioners have stressed the importance of interactive approaches to mitigate the impact of AIDS on agriculture and rural development, sustainable implementation is far from easy and straightforward. This study aims to gain insight into the main lessons and challenges with respect to their design and implementation. Literature review of interactive approaches in agriculture and natural resource management shows that several principles and process guidelines are considered key factors to successful implementation. Although HIV/AIDS does not seem to change these conditions, personal experiences from researchers, development practitioners and extension workers do reveal new and unforeseen challenges. (Contains 3 tables.)