Establishment of health information systems has been a central objective of health sector reform in nearly all LMICs over the last two to three decades. Historically, reform processes have taken introduction of health information systems as inhertently strengthening health sector performance. But today it is more appropriate to talk of health sector strengthening as co-evolving with health information systems strengthening, each reinforcing the performance and reform agendas of the other. The need to build synergies is heightened as there are a multitude of global and national health reform processes underway, like those assoicated with the sustainable development goals or with universal health coverage and each of these have expanded informational needs, requiring robust, flexible, and evolving health information systems. An understanding of the challenges faced by efforts at health systems strengthening helps provide meaningful inputs into health information systems design and vice versa. Such an understanding will enrich public health informatics as an academic discipline, as an area of practice, and as a policy domain.