It is well established that among the many known and tested immunomodulators, polysaccharides isolated from various natural sources occupy a prominent position. β-Glucans belong to a group of biologically active natural compounds called biological response modifiers. These substances represent highly conserved structural components of cell walls in yeast, fungi, grain and seaweed. Its role as an immunomodulator has been well documented for over 50 years. Initial interest in the immunomodulatory properties of polysaccharides was raised after experiments revealed that a crude yeast cell preparation stimulated macrophages via activation of complement. Glucan represents a type of immunostimulant that is active over the full spectrum of biological species, which allowed glucan to be used as a potent immunostimulator in commercially important species such as shrimps, fish or pigs. In the last decade, a renewed interest in human application has brought about some important studies on orally-administered glucan resulting in 18 currently running clinical trials. Fortunately, in the last years, research in reputable laboratories has reached a phase when the basic mechanisms of β-glucan effects are known and the relationship between structure and activity were clearly established. It seems now that β-glucans will finally take a position which was ascribed to them more than fifty years ago.