β-Glucans are structural cell wall polymers of many fungi which possess immunomodulatory activities. Although the therapeutic benefits associated with these compounds, particularly as anti-infective and antitumorigenic agents, have led to a large body of published research over the last five decades, it is still unclear how these carbohydrates mediate their effects. Recent studies, however, are starting to shed some light on the cellular receptors and molecular mechanisms involved, which also have direct relevance on the innate immune response to fungal pathogens.