Carbohydrate-binding lectins play essential roles as pattern recognition receptors in innate immunity in both vertebrates and invertebrates. The carcinolectins 5 (CL5a and CL5b, the CL5 isoforms of horseshoe crab, Carcinoscorpius rotundicauda, with apparent sizes of 36 and 40 kDa, respectively) are prominent plasma lectins that bind all representative microbes and pathogen-associated molecular pattern molecules. Different cDNA isoforms of both CL5a and CL5b were isolated, leading to our speculation on their functional divergence. Characterization of CL5 isoforms bound to microbial cell surfaces demonstrates the diversity of these lectins. The resolution patterns of the isoforms that associate with fungus differ from those that associate with bacteria, suggesting the unique roles these lectins play in the recognition and differentiation of microbes. We postulate that different populations of plasma lectins act in collaboration in frontline innate immune defense against disparate pathogens. The functional diversity of lectins in invertebrates appears to evolutionarily compensate for the lack of acquired immunity.