Antimicrobial peptides are widely expressed in organisms and have been linked to innate and acquired immunities in vertebrates. These compounds are constitutively expressed and rapidly induced at different cellular levels to interact directly with infectious agents and/or modulate immunoreactions involved in defense against pathogenic microorganisms. In invertebrates, antimicrobial peptides represent the major humoral defense system against infection, showing a diverse spectrum of action mechanisms, most of them related to plasma membrane disturbance and lethal alteration of microbial integrity. Marine invertebrates are widespread, extremely diverse, and constantly under an enormous microbial challenge from the ocean environment, itself altered by anthropic influences derived from industrialization and transportation. Consequently, this study reexamines the peptides isolated over the past 2 decades from different origins, bringing phyla not previously reviewed up to date. Moreover, a promising novel use of antimicrobial peptides as effective drugs in human and veterinary medicine could be based on their unusual properties and synergic counterparts as immune response humoral effectors, in addition to their direct microbicidal activity. This has been seen in many other marine proteins that are sufficiently immunogenic to humans, not necessarily in terms of antibody generation but as inflammation promoters and recruitment agents or immune enhancers.