Human beta-defensins are 2-5 kDa, cationic, microbicidal peptides, which represent the first-line host defense against several Gram-negative and Gram-positive bacteria, fungi and viruses. They contain a conserved disulfide-bridge pattern of three pairs of intramolecular cystine bonds. The well-known public health problem related with the growing number of multiresistant bacteria has driven research to look for novel antibiotics, such beta-defensins and a feasible way to produce them. Heterologous expression of beta-defensins could be one way to generate large quantities of beta-defensins for clinical research; however, heterologous expression of beta-defensins has some biochemical problems, such toxicity toward the host cell, peptide degradation by proteolytic cell enzymes, size, folding constrains and low recombinant peptide yields. In this communication, several heterologous systems for producing human beta-defensins are reviewed.