Ocimum sanctum Linn., commonly known as ‘Tulsi’ or ‘Holy Basil’, is considered to be the most sacred herb of India. Several anatomical parts of O. sanctum are known to have an impressive number of therapeutic properties and accordingly find use in several traditional systems of medicine, such as Ayurveda, Unani, and Siddha. Scientific investigations have shown that O. sanctum has a plethora of biological and pharmacological activities. The presence of an impressive number of phytoconstituents in O. sanctum could explain its exceptional beneficial effects. Although several recent articles provide an overview of the various pharmacological properties of O. sanctum, the use of this herb for either prevention or therapy of oncologic diseases has not been exclusively and critically discussed in the literature. The present review critically and comprehensively examines the current knowledge on the chemopreventive and therapeutic potential of O. sanctum. The review also examines, in detail, the biochemical and molecular mechanisms involved in the antineoplastic effects of O. sanctum. Finally, we discuss the role of synergy, current limitations, and future directions of research toward the effective use of this ethnomedicinal plant for the prevention and treatment of human cancer.