We present a matrix of relevant resource utilization domains for use in standardizing applied cost assessment in musculoskeletal conditions. In addition,we highlight the importance of selecting cost categories during the development of an economic evaluation. A set of four steps was applied: (a) literature search identifying economic evaluations in osteoarthritis and osteoporosis, (b) listing and aggregation of cost categories mentioned in the identified articles, (c) development of a matrix of resource utilization domains, and (d) qualitative discussion regarding the generalizability of the matrix to other musculoskeletal conditions such as rheumatoid arthritis. We examined 41 full-length articles (25 cost-of-illness studies or cost-comparisons, 14 cost-effectiveness analyses, and 2 cost-utility analyses), of which 16 studies focused on osteoarthritis and 25 on osteoporosis. The reviewed studies used a total of 151 different cost categories which, after adjustment for synonymous labeling, made up 34 cost categories. A matrix of 16 separate resource utilization domains was developed including seven outpatient, three inpatient, four other disease-related, and two productivity cost domains. We found that cost assessment in economic evaluation in the key musculo-skeletal diseases (osteoarthritis, osteoporosis, and rheumatoid arthritis) is performed rather inhomogeneously. A generalized matrix of applicable resource utilization domains and a flowchart facilitating the development of appropriate resource utilization data have been developed.