Since time immemorial, plants and their compounds have been used in the treatment and management of various ailments. Currently, most of conventional drugs used for treatment of diseases are either directly or indirectly obtained from plant sources. The fungal group of plants is of significance, which not only provides food directly to man but also has been source of important drugs. For instance, commonly used antibiotics are derived from fungi. Fungi have also been utilized in the food industry, baking, and alcohol production. Apart from the economic importance of the microfungi, macrofungi have been utilized directly as food, which is usually got from their fruiting bodies, commonly known as mushrooms. Due to their richness in proteins, minerals, and other nutrients, mushrooms have also been associated with boosting the immune system. This makes mushrooms an important food source, especially for vegetarians and immunosuppressed individuals including the HIV/AIDS persons. In complementary and alternative medicines (CAMs), mushrooms are increasingly being accepted for treatment of various diseases. Mushrooms have been shown to have the ability to stimulate the immune system, modulate humoral and cellular immunity, and potentiate antimutagenic and antitumorigenic activity, as well as rejuvenating the immune system weakened by radiotherapy and chemotherapy in cancer treatment. This potential of mushrooms, therefore, qualifies them as candidates for immunomodulation and immunotherapy in cancer and other diseases' treatment. However, a critical review on mushroom's immune modulating potential in cancer has not been sufficiently addressed. This review puts forward insights into the immune activities of mushroom associated with anticancer activities.