The genus Heliotropium is formed of herbaceous plants belonging to the family Boraginaceae. In Chile and around the world, many Heliotropium species are commonly used in traditional and complementary medicine to treat various diseases. Members of this genus are also recognized for unique biosynthesized phytochemicals, mainly terpenoids, phenolics and alkaloids. Due to important phyto-constituents, as well as their therapeutic potential, many Heliotropium species have been subjected to chemical, biological and pharmacological investigations. This review details the many ethnomedicinal uses for Heliotropium, with an emphasis on Chilean species, and analyzes their scientific validation based on the chemical constituents and pharmacological properties of Heliotropium reported in academic publications. In addition, we discuss the critical conclusions, as well as some suggestions for future phytochemical and biological studies with Heliotropium species.