In this paper, which is dedicated to Dr. Calvin Schwabe, I review the concepts of causation and how they impact on study design, analysis and interpretation of results. Notwithstanding the fact that no observational study can prove causation, there are a number of issues that if addressed sufficiently, can improve the validity and usefulness of our studies. These are elaborated with specific recommendations for the conduct of future observational research. Approaches that have been useful in my teaching and research experience are also described.