Quarantine is an important tool in the armamentarium for protection of the public health from contagious infectious diseases. This chapter reviews the complexities of quarantine related to three separate but tightly linked perspectives: efficacy; legal authority; and ethical, as well as logistical, challenges in implementation. Quarantine has often been used interchangeably with isolation and civil commitment. In the United States, two model public health laws, the Model State Emergency Health Powers Act (MSEHPA) and the Turning Point Model State Public Health Act acknowledge that traditional public health powers such as surveillance, quarantine, and isolation are among the most outdated provisions in existing state laws The WHO addresses the legal issues of quarantine and outlines a collective defense strategy. It published legal guidance in the International Health Regulations 2005 (IHR-2005). The federal government also has the responsibility to assist states in the execution of their quarantine laws.