Interpretation of microbicide trial results has been compromised by challenges to accurate measurement of product adherence and sexual risk behaviors. This article provides an evaluation of the methods used to measure adherence and other sensitive behaviors relevant to assessment of product safety and effectiveness in recently completed trials of vaginal and rectal microbicides. We review the strengths and limitations of existing and novel behavioral measurement strategies and provide recommendations for future trial design with the goal of facilitating the development and identification of safe and effective microbicides for HIV prevention.