Cathelicidins are a family of multi-functional antimicrobial peptides found in almost all types of vertebrates, where they play vital roles in the immune system. As they possess broad-spectrum antimicrobial properties, cathelicidins are not only strongly resistant to Gram-positive and Gram-negative bacteria, fungi, and viruses, but they are also active against many antibiotic-resistant clinical bacteria, adopting a special antimicrobial mechanism that is unlikely to lead to microbial resistance. Cathelicidins likewise possess simple structures, and low hemolytic and cytotoxic activities. Collectively, these features suggest potentially novel and exciting prospects for cathelicidins' application in medicine. Here, we review the structures, classification, activities, mechanisms, as well as prospective developments in the usage and application of cathelicidin antimicrobial peptides.