The past century has seen immense progress in the advancement of methodology to evaluate efficacy of treatment interventions for acute and chronic pain. Continuing challenges revolve around how to best select and measure primary efficacy outcomes for a given analgesic trial. Recognizing the complex, multidimensional, sensory and emotional nature of pain and applying psychometric techniques have facilitated the development of several valid and reliable self-report measures that evaluate pain intensity, pain relief, and other important outcome domains relevant to pain treatment. In the setting of emerging new pain treatment strategies, careful consideration must be given to match current or novel outcome measures to the specific goals of a proposed trial. Future research is needed to directly compare current methods with newer measurement approaches for the critical goal of maximizing validity, reliability, and utility of different outcome measures in clinical trials of pain treatment.