The myocardial extracellular matrix (ECM) is the dynamic environment that is fundamental for the structural and physiological homeostasis of the heart. Alterations in ECM homeostasis may lead to diastolic or systolic dysfunction and consequent development of heart failure (HF). For degradation of ECM, matrix metalloproteinases (MMPs) are responsible. To the most frequently analyzed MMPs in relation to HF syndrome belong MMP-2 and MMP-9. This review summarizes the recent knowledge concerning the role of circulating MMP-2 and MMP-9 (i.e. those that can be determined in blood plasma or serum) in HF, based primarily on papers from human studies. Majority of studies enrolling the higher count of participants suggested that the state of active myocardial remodeling is accompanied by enhanced activation of MMP-2 and MMP-9 and may be also represented by changes in their circulating concentrations. Their levels may be a useful marker for the identification of patients at risk for HF development and poor outcome by themselves, or at the very least as a components of multimarker approach. At the same time MMP-2 and MMP-9 circulating levels can serve as indicators of efficiency of the therapy provided to HF patients, as well as for identification of patients who could profit from particular therapeutic intervention via modification of MMP pathway.