Influenza is a highly contagious airborne disease with a significant morbidity and mortality burden. Seasonal influenza (SI) vaccination has been recommended for healthcare workers (HCWs) for many years. Despite many efforts to encourage HCWs to be immunized against influenza, vaccination uptake remains suboptimal. Sometimes there is a significant sign of improvement, only if numerous measures are taken. Is 'the evidence' and 'rationale' sufficient enough to support mandatory influenza vaccination policies? Most voluntary policies to increase vaccination rates among HCWs have not been very effective. How to close the gap between desired and current vaccination rates? Whether (semi)mandatory policies are justified is an ethical issue. By means of a MEDLINE search, we synthesized the most relevant publications to try to answer these questions. Neither the 'clinical' Hippocratic ethics (the Georgetown Mantra: autonomy, beneficence, non-maleficence, and justice), nor the 'public health' ethics frameworks resolve the question completely. Therefore, recently the 'components of justice' framework was added to the ethical debate. Most options to increase the uptake arouse little ethical controversy, except mandatory policies. The success of vaccination will largely depend upon the way the ethical challenges like professional duty and ethics (deontology), self-determination, vaccine hesitance, and refusal ('conscientious objector') are dealt with.