Starting image analysis with applications to satellite imaging, he became increasingly interested in driving problems from medicine, tackled in close multidisciplinary collaboration between medicine, engineering, and statistics. His research supports a number of clinical imaging research studies with novel, innovative image analysis methodologies related to segmentation, registration, atlas building, shape analysis, and image statistics. Driving clinical problems include research in schizophrenia, autism, multiple sclerosis, Huntington’s disease, Down's syndrome, studies of infants at risk for mental illness, glaucoma, age-related macular degeneration, and in general analysis of anatomical changes due to disease, therapy and recovery. Gerig’s research resulted in various new image analysis methodologies for nonlinear processing, multi-scale segmentation and shape analysis, some of them first and seminal to the field. Applications resulted in new clinical research discoveries such as vulnerability for schizophrenia, differences in brain development in infants with autism, and correlation of shape atrophy with risk status in Huntington’s. New tools and methods are developed as open source software and made available to the public, including teaching materials and hands-on training workshops.