Endothelin-1 (ET-1) is a vasoactive peptide but also mitogenic and pro-angiogenic. ET-1 exerts its actions via two G protein-coupled receptors, ETA and ETB. ET-1 is involved in the progression of prostate cancer. Its actions affect the tumor cell proliferation, inhibition of apoptosis, angiogenesis, migration, invasion, metastasis to the bone growth. Inhibitors of receptors of ET-1 in clinical development are the atrasentan and ZD4054. This article reports on controlled, randomized, phase II and III studies on this new therapeutic class.