This book constitutes the thoroughly refereed post-workshop proceedings of the International Workshop on Brain Lesion, as well as the challenges on  Brain Tumor Segmentation (BRATS), Ischemic Stroke Lesion Image Segmentation (ISLES), and the Mild Traumatic Brain Injury Outcome Prediction (mTOP), held in Athens, October 17, 2016, in conjunction with the International Conference on Medical Image Computing and Computer-Assisted Intervention, MICCAI 2016. The 26 papers presented in this volume were carefully reviewed.  They present the latest advances in segmentation, disease prognosis and other applications to the clinical context.