Ganoderma was considered to be the most valuable medicine in ancient China, and it is still widely esteemed as a valuable health supplement and herbal medicine for the prevention and treatment of a variety of chronic diseases. However, the efficiency of Ganoderma in therapy has long been hindered by the uncertainty of its effectual constituents and the pharmaceutical mechanisms. Lately, it has been found that a most effective pharmaceutical component is the Ganoderma spore. Nevertheless, efficiency in using the spores requires further improvement in processing since the spores have rigid and tough walls the size on a micron scale which are difficult to take up and absorb by the human body. This review describes the top-down approaches in Ganoderma spore processing in order to release the effective pharmaceutical constituents such as the triterpenoid. The production of raw Ganoderma spores, the processing techniques to produce the sporoderm-broken germinating Ganoderma spores, the significant pharmacological activities of Ganoderma, the anti-tumor mechanisms elucidated by modern pharmacological studies, the outcome of the clinical trials, and a prospective of future preparations of triterpenoid-enriched Ganoderma spores and Ganoderma triterpenoids for immune regulation and cancer therapy will be discussed.