Filamentous fungi can secrete large amounts of proteins, glycosylate proteins and grow faster than plant, insect or mammalian cells. With the advances in fungal molecular genetics, strain improvement, and especially fungal genomics, filamentous fungi are developed as microbial cell factories for the production of heterologous proteins. This review focuses on recent developments of filamentous fungi as production hosts, such as protein quality control mechanisms, the secretion pathways, protein modification, strain stability, and most importantly the application of functional genomics in protein expression. At the same time, the strategies for improving heterologous protein production were also discussed in details.