In this commentary, we propose four principles for health policy and systems research in low- and middle-income countries that we think should be ingrained in research practices in this field. These principles are: complementarity of analytical perspectives; interdisciplinarity; cross-cutting knowledge; and theoretical and conceptual foundations. We illustrate each principle with the study of two reforms implemented in sub-Saharan Africa: user fee exemption policies and results-based financing. Taking these four principles into account allows a broader understanding of health systems challenges, and a nuanced approach to reflecting on each of the investigated dimensions. The examples demonstrate the interest of adopting a holistic and systemic approach to researching health systems and policies to go beyond the dominant technocratic vision, often focused on their performance and financing.