BACKGROUND:There is great interest in and excitement about the concept of personalized or precision medicine and, in particular, advancing this vision via various 'big data' efforts. While these methods are necessary, they are insufficient to achieve the full personalized medicine promise. A rigorous, complementary 'small data' paradigm that can function both autonomously from and in collaboration with big data is also needed. By 'small data' we build on Estrin's formulation and refer to the rigorous use of data by and for a specific N-of-1 unit (i.e., a single person, clinic, hospital, healthcare system, community, city, etc.) to facilitate improved individual-level description, prediction and, ultimately, control for that specific unit. MAIN BODY:The purpose of this piece is to articulate why a small data paradigm is needed and is valuable in itself, and to provide initial directions for future work that can advance study designs and data analytic techniques for a small data approach to precision health. Scientifically, the central value of a small data approach is that it can uniquely manage complex, dynamic, multi-causal, idiosyncratically manifesting phenomena, such as chronic diseases, in comparison to big data. Beyond this, a small data approach better aligns the goals of science and practice, which can result in more rapid agile learning with less data. There is also, feasibly, a unique pathway towards transportable knowledge from a small data approach, which is complementary to a big data approach. Future work should (1) further refine appropriate methods for a small data approach; (2) advance strategies for better integrating a small data approach into real-world practices; and (3) advance ways of actively integrating the strengths and limitations from both small and big data approaches into a unified scientific knowledge base that is linked via a robust science of causality. CONCLUSION:Small data is valuable in its own right. That said, small and big data paradigms can and should be combined via a foundational science of causality. With these approaches combined, the vision of precision health can be achieved.