Increased cardiac collagen deposition is observed in almost every cardiac disease and plays an important role in the deteriorating function of the diseased heart. Propeptides of procollagen types I and III, the 2 major collagen types in the heart, can be detected in circulation. Although these propeptides reflect collagen synthesis, also breakdown products of collagen and the matrix metalloproteinases, responsible for the breakdown of the extracellular matrix, can be detected in blood and are used for investigating the turnover of collagen. Clinical trials are performed in recent years to examine the usage of these biomarkers in a diagnostic or prognostic way in heart failure patients. This review aims to discuss the formation of fibrosis, and studies investigating these biomarkers in heart failure are reviewed in this article. In addition, it is conferred what the flaws are of translating these biomarker levels to cardiac fibrosis formation and where we stand in using these biomarkers in clinics.