Reishi owes an exceptional value in nutritional, cosmeceutical, and medical treatments; however, none of the studies has provided its future-driven critical assessment. This study documents an up-to-date
review (2015-2020, wherever applicable) and provide valuable insights (preclinical and clinical evidence-based) with comprehensive and critical assessments. Various databases \'Google scholar\', \'Web of Science\', \'ScienceDirect\', \'PubMed\', \'Springer Link\', books, theses, and library resources were used. The taxonomic chaos of G. lucidum and its related species was discussed in detail with solution-oriented emphasis. Reishi contains polysaccharides (α/β-D-glucans), alkaloids, triterpenoids (ganoderic acids, ganoderenic acids, ganoderol, ganoderiol, lucidenic acids), sterols/ergosterol, proteins (LZ-8, LZ-9), nucleosides (adenosine, inosine, uridine), and nucleotides (guanine, adenine). Some active drugs are explored at an optimum level to make them potential drug candidates. The pharmacological potential was observed in diabetes, inflammation, epilepsy, neurodegeneration, cancer, anxiety, sedation, cardiac diseases, depression, hepatic diseases, and immune disorders; however, most of the studies are preclinical with a number of drawbacks. In particular, quality clinical data are intensely needed to support pharmacological activities for human use. The presence of numerous micro-, macro, and trace elements imparts an essential nutritional and cosmeceutical value to Reishi, and various marketed products are available already, but the clinical studies regarding safety and efficacy, interactions with foods/drinks, chronic use, teratogenicity, mutagenicity, and genotoxicity are missing for Reishi. Reishi possesses many valuable pharmacological activities, and the number of patents and clinical trials is increasing for Reishi. Yet, a gap in research exists for Reishi, which is discussed in detail in the forthcoming sections.