Cardiac hypertrophy is a commonly observed complication of a variety of cardiovascular diseases. As well as mechanical stresses such as pressure overload, several humoral factors may contribute to the development of cardiac hypertrophy. In this chapter, a possible role of locally produced endothelin-1 (ET-1) by cardiomyocytes and cardiac fibroblasts in the mechanism of cardiac hypertrophy is discussed. In the early 1990s, ET-1 was found to induce cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes. Recently, it was further shown that cultured rat cardiomyocytes express abundant preproET-1 (ppET-1) transcripts and release mature ET-1 into their culture medium. Interestingly, cardiomyocyte hypertrophy stimulated by angiotensin II is partially blocked by a receptor antagonist selective for the ETA subtype, suggesting that ET-1 functions as an autocrine/paracrine factor of cardiomyocyte hypertrophy. In addition, it has also been shown that cardiac fibroblasts produce ET-1, that may be relevant to the proliferation of cardiac fibroblasts. Furthermore, there are several reports that suggest a contribution of local ET-1 in the development of cardiac hypertrophy provoked by pressure overload in vivo. From these in vivo and in vitro results, it is suggested that locally produced ET-1 plays an important role in the pathogenesis of cardiac hypertrophy and fibrosis associated with various cardiovascular diseases.