Comparative immunology, derived from zoology and immunology, examines immune systems during evolution. We now know that invertebrates have molecules that share homology with some of those in vertebrates. Acquired immunity first appeared in the vertebrates, but before then innate immune systems had been successfully defending invertebrates and plants against microbial infections for hundreds of millions of years. The germline-encoded receptors of innate systems are relatively limited in diversity and unable to make fine distinctions between closely related structures. Nevertheless, they can recognize certain chemical features shared by groups of microorganisms (e.g., pattern recognition receptors) but not by the host, such as lipopolysaccharide of Gram-negative bacterial cell walls. This capability enables innate immunity to detect the presence of an infection, if not the precise cause—it is thus a biological rather than a structural distinction. Because of its evolutionary success, innate immunity is no longer considered primarily a stopgap measure, a temporary expedient for host defense. It no longer seems to matter that there is an absence of genetic-recombination mechanisms to generate neither specificity nor ‘memory’, because first and second exposures to a microbial substance elicit similar responses. Comparative immunology has enriched the parent field of immunology.