Microscopy remains the cornerstone of the laboratory diagnosis of infections due to blood and tissue parasites. Examination of thick and thin peripheral blood smears stained with Giemsa or other appropriate stains is used for detection and identification of species of Plasmodium, Babesia, Trypanosoma, Brugia, Mansonella, and Wuchereria. Even in the hands of well-trained technologists, diagnosis may be hampered by the sparseness of organisms on the slide and by the subjective nature of differentiating similar-appearing organisms. Microscopy and/or culture of ulcer, bone marrow, tissue aspirate, and biopsy samples are useful for the diagnosis of African trypanosomiasis, onchocerciasis, trichinosis, and leishmaniasis. Serologic assays are available for the diagnosis of a number of these infections, but none of these assays are sensitive or specific enough to be used on their own to establish a diagnosis. In particular, the use of assays for the diagnosis of infection with a particular helminth will often cross-react with antibodies to a different helminth. Very sensitive polymerase chain reaction assays have been developed for a number of these parasites and are available from the Centers for Disease Control and Prevention and from several referral laboratories.