The digital transformation of health care delivery remains an elusive work in progress. Contextual variation continues to be a significant barrier to the development of sustainable health information systems. In this paper we characterize health informaticians as modern alchemists and use this characterization to describe informatics progress in addressing four key healthcare challenges. We highlight the need for informaticians to be diligent and loyal to basic methodological principles while also appreciating the role that contextual variation plays in informatics research. We also emphasize that meaningful health systems transformation takes time. The insight presented in this paper helps informaticians in our quest to develop sustainable health information systems.