Biological agents of concern are a group of highly pathogenic bacteria, viruses, and toxins with the potential to cause significant public health impact in terms of morbidity and mortality, as well as social disruption and public panic, particularly when deployed as a biological weapon. The Centers for Disease Control and Prevention developed a hierarchical classification system for biological agents, ranking specific agents in Categories A, B, and C, where Category A agents are the most virulent and pose the greatest public health threat. This chapter provides detailed descriptions of the Category A agents with special attention to epidemiology, pathogenesis, clinical diagnosis, treatment, and nursing care issues. It provides the healthcare professional with a historical and epidemiologic background as well as a standardized, effective evaluation, and management approach for highly pathogenic viral and bacterial diseases. The chapter introduces biological agents with potential for causing significant human morbidity and mortality.