Host defense peptides are a vital component of the innate immune systems of humans, other mammals, amphibians, and arthropods. The related cationic antimicrobial peptides are also produced by many species of bacteria and function as part of the antimicrobial arsenal to help the producing organism reduce competition for resources from sensitive species. The antimicrobial activities of many of these peptides have been extensively characterized and the structural requirements for these activities are also becoming increasingly clear. In addition to their known antimicrobial role, many host defense peptides are also involved in a plethora of immune functions in the host. In this review, we examine the role of structure in determining antimicrobial activity of certain prototypical cationic peptides and ways that bacteria have evolved to usurp these activities. We also review recent literature on what structural components are related to these immunomodulatory effects. It must be stressed however that these studies, and the area of peptide research, are still in their infancy.