The development of multiple COVID-19 vaccines in record time is a major biomedical achievement, but mechanistic immune correlates of vaccine protection remain to be determined. Most studies on COVID-19 vaccines have focused on neutralizing antibody (NAb) responses, with little emphasis on cellular immunity. However, accumulating data suggest that T cell responses play an important role in vaccine protection against severe COVID-19 disease, particularly against viral variants that partially escape from recognition by NAbs. These insights have implications for using current COVID-19 vaccines and for developing next-generation vaccines against COVID-19 and other infectious diseases.