This book constitutes the refereed proceedings of the 4th International Workshop on Machine Learning in Clinical Neuroimaging, MLCN 2021, held on September 27, 2021, in conjunction with MICCAI 2021. The workshop was held virtually due to the COVID-19 pandemic. The 17 papers presented in this book were carefully reviewed and selected from 27 submissions. They were organized in topical sections named: computational anatomy and brain networks and time series.