Cationic antimicrobial peptides are produced by almost all species of life as a component of their immediate non-specific defense against infections. The assets of these peptides in clinical application include their potential for broad-spectrum activity, rapid bactericidal activity and low propensity for resistance development, whereas possible disadvantages include their high cost, limited stability (especially when composed of L-amino acids), and unknown toxicology and pharmacokinetics. Initial barriers to their success are being increasingly overcome with the development of stable, more cost-effective and potent broad-spectrum synthetic peptides. Thus, there is hope that they will spawn a new generation of antimicrobials with a broad range of topical and systemic applications against infections.