Plants have been one of the important sources of medicines even since the dawn of human civilization. There is a growing demand for plant based medicines, pharmaceuticals, food supplements, health products, cosmetics etc. Pergularia tomentosa L. (Asclepiadaceae) is a perennial twinning herb widely distributed in the Sahara desert, Horn of Africa, Arabian Peninsula to the deserts of southern and eastern Iran, Afghanistan and Pakistan. A wide range of chemical compounds including cardenolides, cardenolide glycoside and taraxasterol-type triterpenes etc. have been isolated from this plant. P. tomentosa has been exploited in traditional medicine as laxative, tumors, warts, depilatory, abortifacient, skin diseases and anthelmintic agents. Moreover, antioxidant, antibacterial, antifungal, insecticidal and cytotoxic activities of this species are documented. The aim of the present review is to summarize and highlight the traditional uses, phytochemical and pharmacological aspects of P. tomentosa.