This article summarizes the structure, funding, organization, and methods of an independent and clinically based surveillance program identifying serious and unrecognized adverse drug events (ADEs). The authors provide a detailed account of the process involved, from investigating a possible serious ADE to disseminating their findings to the Food and Drug Administration (FDA), manufacturers, conferences, journals, and the news media. They also share initial results of their operations with details of 16 drugs associated with serious ADEs, including tabular display of the cases reported and the inconsistencies in the dissemination of safety information. The authors conclude by sharing potential implications of the program’s efforts and how this surveillance method may provide additional opportunity to detect and prevent serious ADEs.