Explaining the diversity of immune reactions requires comparative immunology that takes a phylogenetic view; there is interest in uncovering the underlying mechanisms throughout the animal kingdom. Because of the complexities and diversities of individual phyla, comparative immunology can compare and therefore reveal and elucidate immune mechanisms between and within major groups. There exist two categories of immune responses; 1) nonspecific, innate, natural, non‐adaptive, and non‐anticipatory; 2) induced, adaptive, specific, anticipatory responses. Non‐specific mechanisms include the ubiquitous phagocytosis and encapsulation. In invertebrates, several leukocyte types possess membrane associated markers (e.g. β2m, Thy‐2, Lyt‐, Lyt‐2/3). Transplantation immunity, has revealed various degrees of specificity in sponges, coelenterates, annelids, insects, echinoderms and tunicates. Cytotoxicity is a crucial immunodefense function. Humoral immunity includes naturally occurring and inducible agglutinins, lysozymes, lysins, non‐lysozyme bactericidins, and lysosomal enzymes. Humoral immunity in insects (e.g. cecropins and defen‐sins) that lack specificity and memory, functions efficiently against microbial pathogens. Cytokine‐like molecules, of invertebrates, may regulate host defense responses by an acceptable network similar to that of vertebrates. Communication and recognition molecules are universal since protozoans possess a pheromone (Er‐1) that is related to IL‐2, IL‐1 and TNF‐like activities are found in annelids, mollusks, echinoderms and tunicates. In the future molecular biology must be used extensively to dissect immunodefense more fully, a more modern approach in understanding one component of an organism's totality.