In this chapter, the authors explains genetic, structural and functional relatives of non-fish host defense peptides in fish, and they devote a portion of this discussion to each of these topics. A great leap in understanding host defense peptides in fish came when genetic techniques replaced the previously-utilised tedious and expensive purification techniques, which relied on obtaining large quantity of the biomass sample, homogenising it, and extracting and purifying peptides in a series of multidimensional protein purification steps alongside activity assays. Fish host defense peptides have not received nearly as much attention as their non-fish counterparts. When fish host defense peptides were first discovered, the rare discoveries of active compounds were exciting. The authors conclude by venturing into the realm of speculation about what we anticipate will be discovered in the field of fish host defense peptides in the future.