Secreted frizzled-related proteins (Sfrps) are a family of secreted proteins that bind extracellularly to Wnt ligands and frizzled receptors. This binding modulates the Wnt signaling cascade, and Sfrps interact with their corresponding receptors. Sfrps are thought to play an important role in the pathological mechanism of cardiac disease such as myocardial infarction, cardiac remodeling, and heart failure. However, the overall role of Sfrps in cardiac disease is unknown. Some members of the Sfrps family modulate cellular apoptosis, angiogenesis, differentiation, the inflammatory process, and cardiac remodeling. In this review, we summarize the evidence of Sfrps association with cardiac disease. We also discuss how multiple mechanisms may underlie Sfrps being involved in such diverse pathologies.