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Physical activity has emerged as an important health outcome and its assessment, in particular with objective monitors, has proliferated in recent years. This review considers recent advances in physical activity measurement and clinical trials in cancer and chronic respiratory diseases where physical activity was a primary or key secondary outcome focusing on methodological learning points.There is growing data on (i) the validity of commercial ‘consumer’ physical activity monitors, e.g. FitBit, and (ii) the role of hybrid physical activity assessments; combining objective and subjective measures to understand physical activity quantity and quality. In both cases, adherence is challenging and can be optimized using short monitoring protocols, e.g., 3–4 days, and by providing clear instructions and support materials to participants. Studies in cancer and chronic respiratory disease have found mixed effects from physical activity interventions based on pedometers, behavior change techniques, online resources, and/or therapeutic nutrition. The most responsive physical activity outcomes and minimum clinically important differences are still to be understood.Physical activity measures provide an opportunity to detect changes in health behavior. However, measuring physical activity as a trial endpoint is challenging and focusing effort to ensure optimal participant compliance is important.