Great interest for large-scale production of medicinal mushroom biomass and various pharmaceutically active compounds production dictates the development of comprehensive technologies. Solid state and submerged cultivations in bioreactors represent the most promising technologies for fast and large amount production of medicinal fungi biomass and pharmaceutically active products for human and veterinary need. There are many stages from shaking culture studies to large-scale industrial production. Pilot-scale studies represent the bridge and the balance between the gap of laboratory and industrial scale. Therefore it is not a surprise that most of pilot-scale results and experiences remain uncovered industrial secrets. This chapter is an overview of available engineering achievements in submerged and solid-state cultivation experiences in pilot-scale bioreactors.