Ceramides are sphingolipids and integral components of the eukaryotic cell membrane. Apart from providing structural integrity, ceramides have also been shown to act as second messengers in cell signaling processes. In recent publications, ceramide modulation has been reported in pathological conditions such as cancer, diabetes, Alzheimer's disease (AD), coronary artery disease (CAD), multiple sclerosis (MS), as well as depression. Ceramides or ceramide panel combinations have been proposed as specific disease biomarkers that could be detected in diseased tissue, synovial fluid, cerebrospinal fluid (CSF), and blood. This article reviews ceramide modulation in a selection of different diseases and the potential use of ceramides as biomarkers in diagnostics, determination of disease stage and personalized medicine.