One characteristic abnormality of lesional skin in psoriasis is the excessive production of antimicrobial peptides and proteins (AMPs). AMPs typically are small (12–50 amino acids), have positive charge and amphipathic structure, and are found in all living organisms including mammals, insects, plants and invertebrates. These peptides are best known for their integral role in killing pathogenic microorganisms; however, in vertebrates, they are also capable of modifying host inflammatory responses by a variety of mechanisms. In psoriatic lesions, many AMPs are highly expressed, and especially the associations between psoriasis and cathelicidin, β-defensins or S100 proteins have been well studied. Among them, a cathelicidin peptide, LL-37, has been highlighted as a modulator of psoriasis development in recent years. AMPs had been thought to worsen psoriatic lesions but recent evidence has also suggested the possibility that the induction of AMPs expression might improve aspects of the disease. Further investigations are needed to uncover a previously underappreciated role for AMPs in modulating the immune response in psoriasis, and to improve disease without the risks of systemic immunosuppressive approaches.