Health information exchange (HIE) initiatives are in various stages of development across the United States. They aim to bring previously unavailable clinical data from patients' disparate health records, which may be spread over multiple provider and payer networks, to the point of care where clinicians and their patients need it most. The implications of these initiatives on public health are numerous. This article provides general evaluation methods for measuring the impact of HIE on public health in six use cases: (1) mandated reporting of laboratory diagnoses, (2) mandated reporting of physician-based diagnoses, (3) public health investigation, (4) disease-based non-reportable laboratory data, (5) antibiotic-resistant organism surveillance, and (6) population-level quality monitoring.