The present invention relates to the use of epidermal growth factor receptor (EGFR) antagonists in methods and compositions useful for the treatment of heart disease in a subject. In one embodiment, the methods of the present invention comprise: (a) administering to the subject an EGFR antagonist; and (b) inhibiting or substantially inhibiting the EGFR signal transduction cascade. In another embodiment the method of the present invention may be used in combination with another heart disease therapy.