The introduction of Information Technology (IT) typically comes with the promise of helping to manage scarce resources, increase efficiencies, reduce workload, and increase work productivity. In the context of developing countries, the lure of these promises is magnified given the existing conditions and inefficiencies. International donors for example the World Bank, or the World Health Organization play an important role in shaping this promise because developing countries are dependent on them for both technical and financial aspects. Given that IT projects may take a long time to be fully institutionalized, sufficient resources are required to build the local capacity to support and sustain the project after the withdrawal of donors. Inadequate donor support often contributes to weakening rather than strengthening human resource capacity and effective system design, since it emphasizes the technology itself in the expense of the needs of the users. These factors contribute to the design and implementation of unsustainable health information systems (HIS) in developing countries. Through a comparative case analysis of the HIS in Mozambique and Tanzania, we have identified three sets of relationships as crucial in shaping the sustainability of HIS. The relationships between the Ministry of Health (MoH) and the software development agency, between the MoH and the donors, and between the donors and the software development agency. The reasons for the lack of alignment between the relationships, although possibly different in the two cases, are identified and some specific recommendations are made to support their alignment, and with it, we argue, the sustainability of the system.