This Vaccines issue on "Confidence in Vaccines" provides sound evidence through multiple perspectives of life-saving impacts when vaccination programs are effectively implemented in a population. Yet there remain challenges to achieving this impact, including scientific, medical, manufacturing, policy-related and logistical issues. Additionally, socio-cultural, religious and political agendas can come into play, taking public health hostage and sometimes allowing the circulation of myths regarding vaccination. All of these challenges play a role in public confidence in vaccines and vaccination. What we trust, we embrace. What we do not trust, we do not embrace.