Considering the fact that a key factor in tumor development is the evasion of immune detection, the search for natural products, which have reduced toxicity towards normal tissues as well as immunostimulatory capabilities has received growing interest. One attractive source of antitumor products is the Ganoderma lucidum mushroom, which has been used for centuries as an herbal medicine for the prevention and treatment of a variety of diseases, including cancer, and has been shown to improve immune function. Interestingly, its methanol soluble triterpenoid extracts, namely Ganoderic Acids (GAs), have been the subject of several recent investigations on their chemotherapeutic effects. While current research has revealed GAs' role in inducing apoptosis of cancer cells with a much lower toxicity to healthy cells, little information is available on their in vitro and/or in vivo immune activities. In this review, we aim to discuss the current knowledge on GAs, and their potential as apoptosis inducing as well as immune activating molecules that could be a potential alternative approach for designing novel chemoimmunotherapeutics against malignant diseases. We also discuss other new approaches for exploiting the advantages of using a nanoparticle polymer-GA conjugate as a tool for a sustained and targeted delivery of drug in vivo.