This research falls within the domain of Health Information Systems (HIS) development with particular interest in developing countries. The main objective of the research was to study HIS in order to highlight challenges and opportunities in using Geographical Information System(GIS) for monitoring and management of HIV/AIDS in Malawi. The research studies were done at both the national level (National AIDS Commission and Ministry of Health) and district level(Zomba and Balaka). Qualitative research methods were used which included interviews, document analysis and observations. A GIS prototype was constructed in order to facilitate understanding of practical issues surrounding the intended use of GIS. The research revealed the presence of GIS technology within the Malawian health sector. However, its use has been limited to research with no specific evidence of its use in monitoring and management of HIV/AIDS. In order to understand existing challenges this research draws from the Information Infrastructure theory in terms of installed base, heterogeneity and standardization concepts. The research emphasizes on the need for local capacity for sustainability and scalability of GIS projects. Furthermore, in recognizing the need for cost effectiveness of GIS projects in developing countries the research advocates for setting up infrastructure and building partnerships to facilitate sharing of spatial data between institutions.