This book constitutes the refereed proceedings of the 25th Conference on Medical Image Understanding and Analysis, MIUA 2021, held in July 2021. Due to COVID-19 pandemic the conference was held virtually.  The 32 full papers and 8 short papers presented were carefully reviewed and selected from 77 submissions. They were organized according to following topical sections: biomarker detection; image registration, and reconstruction; image segmentation; generative models, biomedical simulation and modelling; classification; image enhancement, quality assessment, and data privacy; radiomics, predictive models, and quantitative imaging.