In order to improve the repeatability, comparability, and accuracy of MS-based proteomic measurements, there has been considerable international effort to develop appropriate reference materials. Although the majority of reference materials are developed to support measurement quality of routine assays, the development of reference materials for a diverse and changing research field such as proteomics represents unique challenges. In order to define common measurement components and common features of typical proteomic samples, the metrology underpinning proteomics must be considered due to the diversity and changing nature of the field. Reference materials can then be designed around common aspects in order to produce reference materials with the broadest applicability. Reference materials are needed to support both qualitative and quantitative proteomic measurements, involving different design considerations. Consensus and validated statistical approaches to describe the confidence in qualitative measurement, such as protein identification, needs to be established. Common sources of measurement bias also need to be considered in proteomic reference material design.