The objectives of this article were to (1) answer the question of what to measure in a cohort study in which the main focus is the understanding of functioning over time for a specific population and to (2) describe the process of determining what to measure using a theory-informed selection of domains of functioning based on the International Classification of Functioning, Disability and Health (ICF). The Swiss Spinal Cord Injury Cohort Study, a cohort study being carried out in Switzerland for a population of persons with spinal cord injury, was used as an example. A set of domains for the Swiss Spinal Cord Injury Cohort Study was identified demonstrating the application of the methodology. This set consisted of 45 categories of the ICF. Defining what to measure using the ICF is a valuable technique for the cohort researcher because it guarantees comparability of data and comprehensiveness of scope, enhancing the prospects of the study results being understood and is consequently used by health professionals as well as in other contexts, such as in health and social policy.