Summary  This narrative review describes the methodological challenges in the study of dental occlusion. The reigning confusion about the scope of this topic is discussed, and a conceptual framework for understanding dental occlusion research is suggested. The characteristics of clinical studies used in the study of dental occlusion are presented within this proposed framework consisting of a triad comprising the relative positions of the teeth‐mandible‐maxilla, the oral functions and oral appearance. Challenges in the preparation for a clinical study of dental occlusion are reviewed, which include a discourse on the objectives of a clinical study and appropriateness of different study designs. Guidelines are provided for the conduct of studies with a central focus on dental occlusion and diagnostic tests, prognosis, therapy and aetiology, respectively. Summarising chapters present methodological challenges in designing a clinical study of dental occlusion and threats to the proper conduct of a clinical study.