From the beginnings of the civilization, fungi had a significant impact on the history and human activities. Several historical documents regards the involvement of fungi in several and important sectors of human activities, among which foods (e.g. edible and poisonous fungi), magic rituals (e.g. fungi containing psychoactive compounds), art (e.g. drawings and paintings), agriculture (e.g. phytopathogenic fungi), medicine (e.g. antibiotic producing fungi), food preparation (e.g. fermented drinks and bread). As regard the origin of fungi it is lost in the mists of time, and based on recent fossil finds it is traced over 460,000,000 years ago (a very long time before the man appearance on Earth!). This article after reviewing some recent discoveries on fungal origin, reports some representative examples on the role of fungi in history and human activities.