Low-income countries with their funding and implementing partners are increasingly recognizing health information systems (HIS) as an essential way to strengthen and support health systems. There is tremendous potential for innovations in information and communication technologies to assist health managers, health workers, and patients. Yet individual technologies and software applications are often developed without specifying how they will interact and communicate with existing and future information systems. Furthermore, they are developed without giving adequate attention to the needs the information system is supposed to address, resulting in software applications that do not effectively meet user needs. There is a lack of documented systematic methodology for gathering and documenting requirements for developing HIS. This article introduces a systematic, architected, and rational approach (SARA) for the design and development of health information systems. SARA, based on an Enterprise Architecture (EA) approach, represents a portfolio of practices, tools, and methods that can be easily and appropriately adapted and applied in the design phase of health information system development. This article will present early efforts to develop this portfolio including lessons learned from applying SARA in Tanzania.