Invertebrate animals have been used as medicinals for 4,000 years and have served as models for research and teaching since the late 1800s. Interest in invertebrate models has increased over the past several decades as the research community has responded to public concerns about the use of vertebrate animals in research. As a result, invertebrates are being evaluated and recognized as models for many diseases and conditions. Their use has led to discoveries in almost every area of biology and medicine--from embryonic development to aging processes. Species range from terrestrial invertebrates such as nematodes and insects to freshwater and marine life including planarians, crustaceans, molluscs, and many others. The most often used models are the fruit fly Drosophila melanogaster and the minuscule nematode Caenorhabditis elegans. Topics in this article are categorized by biologic system, process, or disease with discussion of associated invertebrate models. Sections on bioactive products discovered from invertebrates follow the models section, and the article concludes with uses of invertebrates in teaching. The models reviewed can serve as references for scientists, researchers, veterinarians, institutional animal care and use committees (IACUCs), and others interested in alternatives to vertebrate animals.