Vaccines have been hailed as one of the greatest success stories of public health in the 20th century. The 20th century also produced a call for evidence-based medicine (EBM) with applications inclusive of preventive health. Since then, several major EBM analyses have called into question vaccine practices well-accepted by physicians, public health officials, and even the lay public. For example, while counter to existing studies and policies, EBM analyses have concluded that data are lacking to support influenza vaccination of healthcare workers to prevent flu complications among the elderly. In this review, we examine the criticisms and consider the shortcomings in the field of vaccinology as well as in the methodology of evidence-based medicine.