The objective of this study was to evaluate the scientific evidence on maitake, including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. This review serves as a clinical support tool. Electronic searches were conducted in 10 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy and lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion and exclusion criteria were used for selection. Grades were assigned using an evidence-based grading rationale. There was a lack of systematic study on the safety and effectiveness of maitake in humans. However, based on popular use and supportive scientific data, three indications are discussed in this review: cancer, diabetes, and immunostimulation. Despite the lack of scientific evidence, maitake mushroom remains a popular agent in commercial products. Future randomized controlled trials are warranted.