New and reemerging infectious diseases, such as pandemic viruses and resistant bacteria, pose a serious threat in the 21st century. Some of these agents represent global security threats. This review provides an overview of diagnostic challenges presented by pandemic influenza and biothreat agents. The article summarizes recent pandemics and disease outbreaks, point-of-care influenza diagnostic tests, biothreat agents, biothreat instrument systems, and technologies in development. It highlights how medical innovation and health care initiatives can help prepare health care professionals and public health personnel to handle future crises. Based on gap analysis for current point-of-care testing deficiencies, it concludes with policy recommendations that will enhance preparedness. (Disaster Med Public Health Preparedness. 2009;3(Suppl 2):S193–S202)