There have been relatively few direct intervention trials of mushroom consumption in humans, although those that have been completed to date indicate that mushrooms and their extracts are generally well-tolerated with few, if any, side-effects. Immunomodulating and anti-tumor effects of mushrooms and their extracts appear to hold potential health benefits. These benefits are primarily due to their polysaccharide content, either in the form of beta-glucans or polysaccharide-protein complexes, which appear to exert their anti-tumorigenic effects by enhancement of cellular immunity via effects on the balance of T helper cell populations and induction of certain interleukins and interferon (IFN)-γ. This review summarizes the current knowledge on edible mushrooms and their components on health outcomes, with a focus on the evaluation of the evidence from human trials. Where information is available from such trials, the active compounds are identified and their proposed mechanisms are discussed.