Certain venues encourage or permit the public to be in contact with animals, resulting in millions of human-animal interactions each year. These settings include county or state fairs, petting zoos, animal swap meets, pet stores, zoologic institutions, circuses, carnivals, educational farms, livestock-birthing exhibits, educational exhibits at schools and child-care facilities, and wildlife photo opportunities. Although human-animal contact has many benefits, many human health problems are associated with these settings, including infectious diseases, exposure to rabies, and injuries. Infectious disease outbreaks reported during the previous decade have been caused by Escherichia coli O157:H7, Salmonella species, Cryptosporidium species, Coxiella burnetii, Mycobacterium tuberculosis, ringworm, and other pathogens. Such infections have substantial medical, public health, legal, and economic effects. This report provides recommendations for public health officials, veterinarians, animal venue staff members, animal exhibitors, visitors to animal venues, physicians, and others concerned with minimizing risks associated with animals in public settings. The recommendation to wash hands is the most important prevention step for reducing the risk for disease transmission associated with animals in public settings. Other critical recommendations are that venues prohibit food in animal areas, venues include transition areas between animal areas and nonanimal areas, visitors receive information about disease risk and prevention procedures, and animals be properly cared for and managed. These updated 2009 guidelines also emphasize risks associated with baby poultry, reptiles, and rodents in public settings, and information about aquatic animal zoonoses has been incorporated.