Ceramides are bioactive lipids that act as secondary messengers for both intra- and inter-cellular signaling. Elevated plasma concentrations of ceramides are associated with multiple risk factors of atherosclerotic cardiovascular diseases and comorbidities including obesity, insulin resistance and diabetes mellitus. Furthermore, atherosclerotic plaques have been shown to be highly enriched with ceramides. Increases in ceramide content may accelerate atherosclerosis development by promoting LDL infiltration to the endothelium and aggregation within the intima of artery walls. Thus, ceramides appear to play a key role in the development of cardiometabolic disease due to their central location in major metabolic pathways that intersect lipid and glucose metabolism. Recently published data have shown that ceramides are not only of scientific interest but may also have diagnostic value. Their independent prognostic value for future cardiovascular outcomes over and above LDL cholesterol and other traditional risk factors have consistently been shown in numerous clinical studies. Thus, ceramide testing with a mass spectrometer offers a simple, reproducible and cost-effective blood test for risk stratification in atherosclerotic cardiovascular diseases.