question: Coronaviruses, members of the order Nidovirales, the largest and most complex of the positive-stranded RNA viruses, have been recognized as important causes of disease in veterinary medicine for nearly a century. In contrast, in human medicine, especially until the recent SARS-CoV-2 pandemic, they were unimportant viruses associated with the common cold. This is a brief comparative review of the biology of coronaviral infections emphasizing the commonalities among the various members of the family and considering how the veterinary experience with coronaviruses can inform the response to SARS-CoV-2. Coronaviruses are perhaps best viewed as mutation machines whose genetic sequences can readily change through genetic drift, recombination, and deletions from a large genome. However, to be of clinical concern, variants must have the perfect set of amino acids in the S protein receptor binding domain and in their replication-mediating nonstructural proteins. Extensive experience with veterinary coronaviral vaccines suggests that optimal clinical immunity is a tandem of mucosal and systemic responses induced by a combination of mucosal and parenteral vaccines.