Poria cocos (Polyporaceae) is a saprophytic fungus that grows in diverse species of Pinus. Its sclerotium, called fu-ling or hoelen, is used in traditional Chinese and Japanese medicine for its diuretic, sedative, and tonic effects. Various studies of this fungus have demonstrated its marked anti-inflammatory activity in different experimental models of acute and chronic inflammation. It is widely used as a constituent of many preparations in Asian medicine, but the number of research papers on its clinical properties is insufficient for establishing its efficacy and safety from a scientific point of view. In this review, we have compiled all the published data concerning the chemistry, pharmacology, and clinical uses of this drug in order to evaluate its clinical interest for future use against various pathologies in which inflammation and immunodepression are implicated. We selected the papers for review on the basis of their ethnopharmacological relevance, using the most relevant databases for the biomedical sciences. Studies on various fungus extracts as well as on the major phytochemical compounds (polysaccharides and triterpenoids) present in Poria cocos comprised the principal objectives of this review. In several of the studies reviewed, the inhibitory effects of triterpenes on phospholipase A2 (PLA2) have been clearly demonstrated. In addition, the inhibitory effects of Poria cocos on the secretion of different cytokines from human peripheral blood monocytes have also been described. Triterpenoids are known to have a pivotal influence on certain diseases such as rheumatoid arthritis, psoriasis, autoimmune uveitis, septic shock, and possibly bronchial asthma, while polysaccharides can potentiate the immune response. Reviewing the literature, we found that polysaccharides from Poria cocos enhanced the secretion of immune stimulators and suppressed the secretion of immune suppressors, thus potentiating the immune response. In addition, they showed antitumor activity against different cancer cell lines. This activity is associated with their capacity to inhibit angiogenesis by downregulating both NF-κB and the induction of NF-κB/Rel translocation.