β-Glucan is a well-known biological response modifier (BRM) that has been used as an adjuvant therapy for cancer since 1980, primarily in Japan. It represents a class of fungal cell wall polysaccharides that are made up entirely of glucose that is β(1-3)-linked together in linear chains with a variable frequency of β(1-6)-linked side chains. β-glucans from cereal grains such as oats or barley can have a similar BRM activity in tumor models but contain linear chains with β(1-4)-linkages in addition to β(1-3)-linkages. β-Glucans also enhance the innate host defense against certain bacteria, yeast, and viral pathogens. In the 1990s, there were attempts in the U.S. to develop a yeast β-glucan as an anti-infective BRM. In addition, β-glucans are also considered to be important in prophylaxis against irradiation. In summary, β-glucan might be the most in important natural immunomodulator.