Collectively, the endothelins and their receptors — referred to as the endothelin (ET) axis — have key physiological functions in normal tissue, acting as modulators of vasomotor tone, tissue differentiation, development, cell proliferation and hormone production. Based on new data, the ET axis also functions in the growth and progression of various tumours. Preliminary results from clinical trials, such as those with atrasentan — an ET_A-receptor antagonist — in prostate cancer, are encouraging. The place of ET-receptor antagonists in cancer therapy for a range of malignancies merits further investigation.