Osteoporosis is an important public health challenge. Several medicinal mushrooms are able to improve bone stability by influencing different steps of bone formation, mineralization, or resorption. In nearly all investigations, the effects have been shown in vitro or in animal assays and only very few in clinical studies. Positive results exist for medicinal mushrooms of the genera Cordyceps/Ophiocordyceps, Ganoderma, Grifola, Lentinula, Phellinus, Pleurotus, Taiwanofungus, Trametes, and Wolfiporia. The results for Hericium are not consistent. This article critically reviews these investigations and describes challenges for the future.