IntroductionMushrooms have been regarded as gourmet cuisine across the globe since antiquity for their unique taste and subtle flavor. Recently, it has been discovered that many mushroom species are miniature pharmaceutical factories producing hundreds of novel constituents with miraculous biological properties. They have a long history of use in Oriental medicine, but their legendary effects in promotion of good health and vitality are being supported by contemporary studies only. Of late, mushrooms have emerged as wonderful source of nutraceuticals, anti-oxidants, anti-cancer, prebiotic, immunomodulating, anti-inflammatory, cardiovascular, anti-microbial, and anti-diabetic. The ongoing research projects are aimed to promote mushrooms as new generation "biotherapeutics".Cancer is a leading cause of death worldwide. The current anti-cancer drugs available in market are not target specific and pose several side-effects and complications in clinical management of various forms of cancer, which highlights the urgent need for novel effective and less-toxic therapeutic approaches. In this context, some prized mushrooms with validated anti-cancer properties and their active compounds are of immense interest. Numerous clinical trials have been conducted to assess the benefits of using commercial preparations containing medicinal mushroom extracts in cancer therapy. Their potential uses individually and as adjuncts to cancer therapy have emerged. Mushrooms are known to complement chemotherapy and radiation therapy by countering the side-effects of cancer, such as nausea, bone marrow suppression, anemia, and lowered resistance. Recently, a number of bioactive molecules, including anti-tumor agents, have been identified from various mushrooms. The bioactive compounds of mushrooms include polysaccharides, proteins, fats, ash, glycosides, alkaloids, volatile oils, tocopherols, phenolics, flavonoids, carotenoids, folates, ascorbic acid enzymes, and organic acids. The active components in mushrooms responsible for conferring anti-cancer potential are lentinan, krestin, hispolon, lectin, calcaelin, illudin S, psilocybin, Hericium polysaccharide A and B (HPA and HPB), ganoderic acid, schizophyllan, laccase, etc. Polysaccharides are the best known and most potent mushroom-derived substances with anti-tumor and immunomodulating properties. The polysaccharide, β-glucan is the most versatile metabolite due to its broad spectrum biological activity. These β-glucans consist of a backbone of glucose residues linked by β-(1 → 3)-glycosidic bonds, often with attached side-chain glucose residues joined by β-(1 → 6) linkages. Their mechanisms of action involve their being recognized as non-self molecules, so the immune system is stimulated by their presence. Hispolon, an active polyphenol compound, is known to possess potent anti-neoplastic properties and potentiate the cytotoxicity of chemotherapeutic agents. The scientific investigations to back the claims have gained momentum in recent years. Findings suggest that some mushrooms in combination with commercial anti-cancer drugs work in synergy as an effective tool for treating drug-resistant cancers. In this study, the mechanisms underlying apoptosis induced by medicinal mushrooms are summarized. This compilation is expected to provide new insights into the possible therapeutic use of the mushroom extracts against different cancers. These results are significant in that they provide a mechanistic framework for further exploration of the use of bioactive compounds as novel anti-tumor agents. The purpose of the present review is to summarize the available information and to reflect the current status of this research area with a view for future direction.