In spite of billions of dollars expended on cancer research every year, the incidence rate and the mortality rate due to this widespread disease has increased drastically over the last few decades. Recent reports from the World Health Organization advocate that overall global cancer burden and deaths due to cancer are expected to double by the next decade. Synthetic drugs developed as chemotherapeutics have repeatedly shown adverse side effects and development of chemoresistance. Cancer is basically a multifactorial disease that necessitates the modulation of multiple targets and oncogenic signaling pathways. Honokiol (CHO) is a biphenolic natural compound isolated from the leaves and barks of Magnolia plant species and has been extensively studied for its beneficial effects against several chronic diseases. Honokiol is capable of efficiently preventing the growth of wide variety of tumors such as those of brain, breast, cervical, colon, liver, lung, prostate, skin, and hematological malignancies. Recent work has shown that this phytochemical can modulate various molecular targets such as activation of pro-apoptotic factors, suppression of anti-apoptotic proteins and different transcription factors, downregulation of various enzymes, chemokines, cell surface adhesion molecules, and cell cycle proteins, and inhibition of activity of protein tyrosine kinases and serine/threonine kinases. Because of its pharmacological safety, honokiol can either be used alone or in combination with other chemotherapeutic drugs for the prevention and treatment of cancer. The current review describes in detail the various reports supporting these anti-cancer studies documented with this promising agent.