Host defense peptides (HDPs) are a large group of innate immune effectors that are also termed antimicrobial peptides. Because of the rapid progress that has been made in completing several animal genomes, many HDPs have been systemically defined using bioinformatic analysis and partially characterized using reverse genomic approaches. In pigs, about 30 HDPs have been identified and partially characterized relative to structure and function. Antimicrobial activity of porcine HDPs has been extensively evaluated against a broad spectrum of microorganisms in vitro and evaluated for their protective role in vivo. Increasing evidence indicates that HDPs are functionally differentiated during posttranslational and postsecretory processing, and that the structural units for antimicrobial and immunoregulatory functions are separate. These findings suggest promising new avenues for therapeutic drug design based on HDPs, including porcine HDPs. This review summarizes and discusses advances in porcine HDPs research during the last decade with an emphasis on the rapidly expanding profiles and biological functions.