Accurate, reliable detection of infectious agents, as well as the resulting disease is critical for many aspects of wildlife management. This usually requires laboratory examination of specimens, either from animals found sick or dead in the field, or collected from live animals for testing. The planning and implementation of the sampling—starting with specimen collection, through analysis of the specimens, to interpretation of the test results—are extremely important for overall quality of the study, and should be done collaboratively, involving both wildlife biologists and laboratory diagnosticians. The choice of diagnostic test(s) to be used is central to the process, as it determines the type of sample to be collected, how samples are handled, and the conclusions that can be drawn from the test results. Often, however, owing to the relative rarity of wildlife disease analyses, and because of the variation stemming from host species physiology, wildlife tests are not as well validated as for domesticated animals. When this occurs, interpretation of results may be flawed. This chapter reviews the methodological steps required to establish an effective and unbiased wildlife disease testing protocol.