Infection with a parasite/pathogen and the resulting disease are two distinct phenomena and should not be confused. Establishing a relationship between an infectious agent and a disease is a fundamental epidemiological task that requires careful observational and experimental studies. This chapter evaluates some of the basic approaches and attendant challenges in documenting the presence of infection and disease in a wildlife population. Furthermore, the text also discusses the different types of relevant investigation, including observational, cross-sectional, and cohort studies, which can be used to quantify the frequency of occurrence of a pathogen in a wildlife population.