The widespread occurrence of biological activities within the fungal kingdom is now widely accepted. Since ancient times the so called mushrooms meaning Basidiomycota have been used for medicinal purpose. All major human body functions were considered to benefit from fungi intake. These positive effects include prophylactic as well as curative actions. Historically, Oriental countries first recognized mushrooms as an important source of medicines. Recently, Occidental research starts to really consider this almost untapped source of therapeutic drugs. Indeed, discovering new major medics is becoming a great challenge. The aim of the present review is to outline past and current major therapeutic interests and pharmacology of medicinal mushrooms, and their applications in human health care. Indeed, metabolites from Basidiomycota demonstrate verified pharmacological activity in major diseases such as chronic inflammation, oxidation associated pathologies, diabetes, infections (HIV, fungi, bacteria), immune system disorder and cancer.