The beneficial properties of β-glucan in cancer therapy have been recognized for centuries. Their proposed mechanism of action occurs mainly via stimulation of macrophages and priming of neutrophil complement receptor 3 (CR3) for eliciting CR3-dependent cellular cytotoxicity of iC3b-opsonized tumor cells. Recent studies revealed that β-glucans may also promote anti-tumor T cell responses. Thus, β-glucan-mediated tumor immunotherapy may engage both the innate and adaptive anti-tumor immune reponses to restrain tumor progression. In this Chapter, we will describe the mechanism of action of β-glucan in cancer immunotherapy and discuss the available data from current β-glucan clinical trials. The potential challenges for this therapy will be also discussed. It is proposed that a biological response modifer β-glucan can serve as a potent adjuvant to specifically modulate both the innate and adaptive immune cells.