Ischemic heart disease is a rapidly increasing common cause of death in the world. This disease is the insufficient status of oxygen within the cardiac muscles due to an imbalance between oxygen supply and demand, and a cardiac disease that occurs as a result of coronary artery stenosis. Conventional surgery-based therapy for the treatment of ischemic heart diseases has been advanced with biopharmaceutical-based therapy, such as protein, gene and cell therapy. The conventional medical therapy focuses on the use of drug eluting stents, coronary-artery bypass-graft surgery and anti-thrombosis. Biopharmaceutical-based therapies including recombinant protein therapy, gene therapy and cell transplantation are recognized as promising approaches in inducing neovascularization and improving collateral blood flow in the ischemic heart. This review explores the current status and future of the treatment of ischemic heart diseases with conventional medical therapy, biopharmaceutical-based therapy focused on the proteins and polymeric hydrogels for delivery of therapeutic proteins.