Ganoderma genus comprises one of the most commonly studied species worldwide, Ganoderma lucidum. However, other Ganoderma species have been also reported as important sources of bioactive compounds. Polysaccharides are important contributors to the medicinal properties reported for Ganoderma species, as demonstrated by the numerous publications, including reviews, on this matter. Yet, what are the chemical features of Ganoderma polysaccharides that have bioactivity? In the present manuscript, the chemical features of Ganoderma polysaccharides with reported antioxidant, antitumor and antimicrobial activities (the most studied worldwide) are analyzed in detail. The composition of sugars (homo- versus hetero-glucans and other polysaccharides), type of glycosidic linkages, branching patterns, and linkage to proteins are discussed. Methods for extraction, isolation and identification are evaluated and, finally, the bioactivity of polysaccharidic extracts and purified compounds are discussed. The integration of data allows deduction of structure-activity relationships and gives clues to the chemical aspects involved in Ganoderma bioactivity.