Accumulating evidence has suggested that epigenetic alternations are as important as genetic mutations in cancer development. It is proposed that tumors are arisen by "malignant reprogramming" driven by a combination of both genetic and epigenetic changes. It therefore comes as no surprise that histone demethylases, the newest members of the histone modifying enzymes, are found to be targets of mutations and dysregulation in cancer cells. In this review article, we provide an overview of the types of histone demethylases whose genetic structure or expression is altered in cancers, the action of histone demethylases in cancer development and their potential inhibitors. Special emphasis is placed on the roles of histone demethylases in prostate cancer progression.