Antimicrobial peptides (AMPs) could evolve into new therapeutic lead molecules against multi-resistant bacteria. As insects are a rich source of AMP, the identification and characterization of insect-derived AMPs is particularly emphasized. One challenge of bringing these molecules into market, e.g., as a drug, is to develop a cost-efficient large-scale production process. Due to the fact that a direct AMP isolation from insects is not economical and that chemical synthesis is recommended for peptide sizes below 40 amino acids, a viable option is heterologous AMP production. Therefore, previous knowledge concerning the expression of larger proteins can be adapted, but due to the AMP nature (e.g., small size, bactericide) additional challenges have to be faced during up and downstream processing. Nonetheless the bottleneck for large-scale AMP production is the same as for proteins; mainly the downstream process. This review introduces opportunities for insect-derived AMP production, like the choice of the expression system (based on previously derived data), depending on the AMP nature, as well as new purification strategies like elastin-like peptide/intein based purification strategies. All of these aspects are discussed with regard to large-scale processes and costs. (c) 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:1-11, 2015