The presence and extent of coronary artery calcification (CAC) is established in primary prevention since the CAC score is the single best predictor of future cardiovascular events. While CAC progresses with increasing age, individual CAC progression can be estimated based on the subject’s age, gender, and CAC percentile at first examination. To date, several algorithms and methods for the definition of CAC progression are available in the literature. Increased CAC progression is associated with traditional cardiovascular risk factors including hypertension, diabetes, and smoking status. Also, lipid-lowering therapy may influence the progression of CAC. Epicardial adipose tissue is a further cardiovascular risk marker that may lead to intensified CAC progression if its volume increases. In terms of clinical implications, initial data suggest that extensive CAC progression is linked to worse outcome; however, further studies are needed to establish this relationship and to define appropriate time intervals between repetitive examinations. This review article gives an overview of the existing literature with an emphasis on various definitions of CAC progression, predictors of increased CAC progression, as well as clinical implications.