Creosote bush, Larrea tridentata, is known as chaparral or greasewood in the United States and as gobernadora or hediondilla in Mexico. Nordihydroguaiaretic acid (NDGA), the main metabolite of the creosote bush, has been shown to have promising applications in the treatment of multiple diseases, including cardiovascular diseases, neurological disorders and cancers. Creosote bush is a promising agent of North American herbal medicine, and it has extensive pharmacological effects and specific mechanisms of actions. This review provides an update of recent in vitro and in vivo research about NDGA and describes experimental studies using NDGA as antioxidant. Also, potential medical uses based on the effects of NDGA on the cardiovascular, immune and neurological systems; cancer; tissue engineering; as well as pharmacokinetics and toxicity are discussed.