This book constitutes the refereed proceedings of the 5th International Workshop on Machine Learning in Medical Imaging, MLMI 2014, held in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention, MICCAI 2014, in Cambridge, MA, USA, in September 2014. The 40 contributions included in this volume were carefully reviewed and selected from 70 submissions. They focus on major trends and challenges in the area of machine learning in medical imaging and aim to identify new cutting-edge techniques and their use in medical imaging.