Polysaccharides are the most abundant bioactive compounds in Ganoderma and have been widely used as dietary supplements in traditional Chinese medicine for thousands of years. Polysaccharides from Ganoderma exhibit unique biological properties, including anti-tumor, anti-inflammatory, and immunomodulatory activities. Herein, the sources and structures of polysaccharides from Ganoderma were presented. This work also reviews the immunomodulatory activities and possible mechanisms of polysaccharides from Ganoderma on different immune effector cells, including lymphocytes and myeloid cells. As an available adjunctive remedy, polysaccharides from Ganoderma can potentially be applied for the modulation of the host immune system, namely the innate immunity, the cellular immunity, and the humoral immunity.