The naturally occurring homo-polyamide biopolymer, epsilon-poly-L-lysine (epsilon-PL) consists of 25-35 L-lysine residues with amide linkages between alpha-carboxyl groups and epsilon-amino groups. epsilon-PL exhibits several useful properties because of its unusual structure, such as biodegradability, water solubility, no human toxicity, and broad-spectrum antibacterial activities; it is widely applied in the fields of food, medicine, clinical chemistry and electronics. However, current industrial production of epsilon-PL is only performed in a few countries. Based on an analysis of the physiological characteristics of epsilon-PL fermentation, current advances that enhance epsilon-PL fermentation, from strain improvement to product isolation are systematically reviewed, focusing on: (1) elucidating the metabolic pathway and regulatory mechanism of epsilon-PL synthesis; (2) enhancing biosynthetic performance through mutagenesis, fermentation optimization and metabolic engineering; and (3) understanding and improving the biological activity and functional properties of epsilon-PL. Finally, perspectives on engineering and exploiting epsilon-PL as a source material for the production of various advanced materials are also discussed, providing scientific guidelines for researchers to further improve the epsilon-PL fermentation process.