We live in a world populated by an enormous number of micro-organisms. This necessitates the existence of highly effective mechanisms to control microbial growth. Through many research efforts, a chemical defense system based on the production of antimicrobial proteins (AMPs) has been identified. AMPs are endogenous, small proteins exhibiting antimicrobial activity against a wide variety of micro-organisms. The wide distribution of these molecules in the plant and animal kingdom reflects their biological significance. Various human AMPs show a potent effect on pathogenic micro-organisms including antibiotic-resistant bacteria. Thus, there is great interest in understanding the role of AMPs within innate immunity and evaluating their use and/or specific induction to fend off infections. In this review, we provide an overview of the characteristics of human AMPs and discuss examples where AMPs may be involved in the pathogenesis of infectious and inflammatory diseases.