Endothelin and its two different cognate receptors have been implicated in a wide variety of pathophysiological conditions since it was first identified as a vasoactive local hormone.Especially in the last decade, the studies revealed that the aberrant expression of endothelin axis has critical importance in the cancer biology involving in neovascularization, cellular survival, metastasis as well as drug resistance, by taking part in different signalling mechanisms within the cell. This situation has attracted the attention of many scientists to investigate not only reveal the molecular mechanistic role of endothelin axis in cancer pathophysiology but also design new drugs targeting the endothelin axis. Further studies suggest that utilizing endothelin axis as a new diagnostic parameter to define malignant features and monitor the prognoses of cancer This study, which was compiled from both preclinical and clinical studies, was prepared to provide an overview of the potential role of the endothelin axis in cancer biology, as well as an overview of the drugs developed against the endothelin axis