RNA helicases constitute a large group of essential enzymes involved in all aspects of RNA metabolism. With few exceptions, human RNA helicases of DDX and DHX gene families have not been well characterized. However, several of them have been shown to be dysregulated in cancer, including over-expression in various types of tumors. Although the exact contribution of RNA helicases to carcinogenesis has not been determined, their over-expression in cancer render them potential targets for novel anti-cancer agents. In this review, RNA helicases whose expression is up-regulated in cancer are highlighted.