Fungi are widely used as cell factories for the production of pharmaceutical compounds, enzymes and metabolites. Fungi form colonies that consist of a network of hyphae. During the last two decades it has become clear that fungal colonies within a liquid culture are heterogeneous in size and gene expression. Heterogeneity in growth, secretion, and RNA composition can even be found between and within zones of colonies. These findings imply that productivity in a bioreactor may be increased by reducing the heterogeneity within the culture. The results also imply that molecular mechanisms underlying productivity of fungi in bioreactors should not be studied at the culture level but at the level of micro-colony populations or even at zonal or hyphal level.