The accurate measurement of organic compounds in a wide variety of matrices is important to a great number of sectors including health, the environment, forensics, food safety, pharma. The instruments used to make such measurements require calibration, and for well-defined chemical entities the calibration hierarchy leads to a pure material that has been value-assigned for the mass fraction of the analyte within the material. Such organic primary reference materials are provided as Certified Reference Materials (CRMs) by National Metrology Institutes. This paper reviews the various methods that can be used to value-assign such reference materials, both for small organic molecules such as valine and folic acid, as well as larger molecules such as peptides.