Estradiol and testosterone measurements are widely used to assess steroid hormone status and to monitor stimulative, suppressive, or replacement therapy among children and adults of both sexes. Despite their common application, these measurements – particularly at low concentrations – show only limited comparability among assays, such as those observed for testosterone among women or for estradiol among postmenopausal women. This shortcoming hampers progress in research and in research translation. To overcome this, the Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences (CDC/NCEH/DLS) initiated a project to standardize and to improve steroid hormone measurements. The project is a collaborative effort between institutions, organizations, and groups involved in estradiol and testosterone testing, test interpretation, and use. Specific activities are scheduled based on needs assessments conducted with the clinical, research, and public health communities. The initial focus of this standardization project is to improve analytical measurements through reference laboratory activities. As part of the project’s translational activities, CDC/NCEH/DLS will work further with professional societies and organizations to improve pre- and postanalytical issues that affect results from these measurements and their interpretation.