ABSTRACT: The present work uses fossils and subfossils to decipher the origin and evolution of terrestrial pathogens and endoparasites. Fossils, as interpreted by morphology or specific features of their hosts, furnish minimum dates for the origin of infectious agents, coevolution with hosts, and geographical locations. Subfossils, those that can be C14 dated (roughly under 50,000 years) and are identified by morphology as well as molecular and immunological techniques, provide time periods when humans became infected with various diseases. The pathogen groups surveyed include viruses, bacteria, protozoa, fungi, and select multicellular endoparasites including nematodes, trematodes, cestodes, and insect parasitoids in the terrestrial environment. 1. Introduction The world is filled with pathogens that have been around for millions of years, yet we know very little about their origins and evolution. The present work uses fossils and subfossils to decipher the origin and evolution of terrestrial pathogens and endoparasites. Fossils furnish minimum dates for the origin of infectious agents, coevolution with hosts, and geographical locations. Subfossil remains, those that can be C14 dated (roughly under 50,000 years), provide time periods when humans became infected with various diseases. The detection of fossil infectious agents is based on morphology or specific features of their hosts while molecular and immunological techniques can be used as well in searching for subfossil pathogens and parasites. Arthropods in amber that were vectoring vertebrate pathogens have provided unique information on the origin and evolution of human and animal diseases [1]. Such detailed preservation is due to the instant death of the vector, its rapid desiccation, and impregnation by natural fixatives. Dates for the various amber sites mentioned in the present work are Dominican, 20–15？mya based on foraminifera and 45–30？mya based on coccoliths; Mexican, 22–26？mya; Baltic, 40–50？mya; Myanmar (Burmese), 97–110？mya; and Lebanese, 130–135？mya. The pathogen groups surveyed include viruses, bacteria, protozoa, and fungi in the terrestrial environment. Also included are multicellular endoparasites such as nematodes, trematodes, cestodes, and select insect parasitoids. Examples are included when both the pathogen/parasite and host occur together as determined by morphological, molecular, or immunological evidence. Reports of disease in the fossil record based on host signs have been summarized previously [2–4]. 2. Pathogens 2.1. Viruses Viruses are probably quite ancient and may have existed