Recent studies have shown a significant degree of molecular polymorphisms in many nonspecific immune molecules, which were believed to be conserved due to the limited variance in the germline genes. The polymorphisms in γ/δ T cell receptor, B1 cell receptor and certain innate immune components have been found in vertebrates, whereas the polymorphisms in certain immunoglobulin superfamily molecules, antimicrobial peptides and pattern recognition receptors were identified in invertebrates. Similar to that was found for the specific immune molecules, the polymorphisms in non-specific immune molecules derived from gene rearrangement, single nucleotide polymorphisms, DNA mutation and alternative splicing of exons. The polymorphisms of immune molecules in invertebrates form the molecular basis to recognize and defend against different pathogens in lower organisms, and contributed in adaptive evolution. In this review, we will discuss recent progress in the polymorphism studies on the functions of invertebrate immune molecules and their possible formation mechanisms.