As providers of frontline clinical care for patients with acute and potentially life-threatening infections, emergency departments (EDs) have the priorities of saving lives and providing care quickly and efficiently. Although these facilities see a diversity of patients 24 hours per day and can collect prospective data in real time, their ability to conduct timely research on infectious syndromes is not well recognized. EMERGEncy ID NET is a national network that demonstrates that EDs can also collect data and conduct research in real time. This network collaborates with the Centers for Disease Control and Prevention (CDC) and other partners to study and address a wide range of infectious diseases and clinical syndromes. In this paper, we review selected highlights of EMERGEncy ID NET's history from 1995 to 2017. We focus on the establishment of this multisite research network and the network's collaborative research on a wide range of ED clinical topics.