Glycogen synthase kinase-3 (GSK-3) is a cytoplasmic serine/threonine protein kinase which is known to regulate a variety of cellular processes through a number of signaling pathways important for cell proliferation, stem cell renewal, apoptosis and development. Although GSK-3 exists in a variety of tissues, this kinase plays very important roles in the heart to control its development through the formation of heart and cardiomyocyte proliferation. GSK-3 is also recognized as one of the main molecules that control cardiac hypertrophy and fibrosis. Therefore, GSK-3 could be an attractive target for the development of new drugs to cure cardiac diseases. The present review summarizes the roles of GSK-3 in the signaling pathways and the heart, and discusses the possibility of new drug development targeting this kinase.