COVID-19 has created global challenges that only an effective vaccine, apparently, can lead the citizens of the world back to a sense of normalcy. While safe vaccines were developed, tested and approved at an extraordinary pace, concerns were raised regarding the public's response in accepting the vaccine on the population level. Israel was among the first countries to roll out a massive national campaign for COVID-19 vaccination, positioning Israel as the global lead in vaccine uptake. Priority for vaccination was given to high-risk groups: older and middle-age adults, healthcare workers, senior home residents and caregivers, people with chronic conditions, followed by teachers and soldiers. Contributing to the success of the operation thus far has been a systems approach beyond nationwide accessibility: building public trust through an integrated and familiar health system, a familiar technology (vaccine), transparency regarding vaccine safety information, culturally appropriate messages in digital and offline media, acknowledging diverse health literacy needs, and active participation and role-modeling by political/religious opinion leaders. Vaccine resistance and hesitancy may be encountered as the campaign progresses, and younger groups targeted. Future considerations include perceived benefits offered to people with vaccination and the role of health/digital literacy in preparedness policies. Ethical issues regarding the rights of those vaccinated, as well as those who have not, are explored.