The conference on which this supplement reports was organized to bring together microbicide researchers with researchers in the areas of drug prophylaxis and therapeutics development. The goal of session 1 was to share methods used to validate markers of disease, elucidate the logic used to substantiate the performance of those markers, and identify ways to translate this experience into practical steps for developing microbicides. The experiences discussed ranged from de novo discovery of new therapeutics to qualification of biomarkers across all stages of development, and covered the complexity of biomarker identification, use, and assessment in the clinical areas of cancer and infectious disease. This review is based on the presentations of Drs. Harsukh Parmar (AstraZeneca), Sudhir Srivastava (National Cancer Institute [NCI]), and Juan Leal (Exelixis Inc.), and the subsequent discussion led by Drs. Sam Niedbala (Lehigh University) and Thomas Moench (ReProtect) during a background session held at the conference entitled "Biomarkers for evaluation of vaginal microbicides and contraceptives: Discovery and early validation," organized by CONRAD and the Alliance for Microbicide Development in November 2006.