The substitution of materia medica in Tibetan medicine was an important issue in the past, and still is today. This article will offer a brief survey of references found in Tibetan written sources, and discuss the only three Tibetan treatises that deal exclusively with the subject. It will explore the underlying modes of substitution, and provide insights into the criteria that are used to determine suitable substitutes. Ultimately it will be demonstrated that one can distinguish seven criteria--namely the taste, healing potential, type, substance, name, shape, and smell--that are used to determine an appropriate substitute for rare or expensive materia medica in the Tibetan medical tradition.