| Summary: | <i>Cordyceps militaris</i> is an entomopathogenic ascomycete with similar pharmacological importance to that of the wild caterpillar fungus <i>Ophiocordyceps sinensis</i>. <i>C. militaris</i> has attracted significant research and commercial interest due to its content in bioactive compounds beneficial to human health and the relative ease of cultivation under laboratory conditions. However, room for improvement exists in the commercial-scale cultivation of <i>C. militaris</i> and concerns issues principally related to appropriate strain selection, genetic degeneration of cultures, and substrate optimization. In particular, culture degeneration—usually expressed by abnormal fruit body formation and reduced sporulation—results in important economic losses and is holding back investors and potential growers (mainly in Western countries) from further developing this highly promising sector. In the present review, the main factors that influence the generation of biomass and metabolites (with emphasis on cordycepin biosynthesis) by <i>C. militaris</i> are presented and evaluated in conjunction with the use of a wide range of supplements or additives towards the enhancement of fungal productivity in large-scale cultivation processes. Moreover, physiological and genetic factors that increase or reduce the manifestation of strain degeneration in <i>C. militaris</i> are outlined. Finally, methodologies for developing protocols to be used in <i>C. militaris</i> functional biology studies are discussed.
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