Squalene is a natural lipid belonging to the terpenoid family and a precursor of cholesterol biosynthesis. It is synthesized in humans and also in a wide array of organisms and substances, from sharks to olives and even bran, among others. Because of its significant dietary benefits, biocompatibility, inertness, and other advantageous properties, squalene is extensively used as an excipient in pharmaceutical formulations for disease management and therapy. In addition, squalene acts as a protective agent and has been shown to decrease chemotherapy-induced side-effects. Moreover, squalene alone exhibits chemopreventive activity. Although it is a weak inhibitor of tumor cell proliferation, it contributes either directly or indirectly to the treatment of cancer due to its potentiation effect. In addition, squalene enhances the immune response to various associated antigens, and it is therefore being investigated for vaccine delivery applications. Since this triterpene is well absorbed orally, it has been used to improve the oral delivery of therapeutic molecules. All of these qualities have rendered squalene a potentially interesting excipient for pharmaceutical applications, especially for the delivery of vaccines, drugs, genes, and other biological substances. This paper is the first review of its kind and offers greater insight into squalene's direct or indirect contribution to disease management and therapy.