COVID-19 is the largest pandemic in the past century since the influenza outbreak of 1918. It has resulted in countless lives lost, widespread suffering, economic ruin to many and caused major upheavals in our way of life. Vaccination is a key enabler to end this epidemic. In what was the shortest time from pathogen identification to effective vaccination in human history, numerous countries have experienced the powerful positive effect of vaccination on their population. Reports of rare but serious adverse reactions, vaccine escape variants, vaccine hesitancy and logistic hurdles have dampened our march towards herd immunity. In this article, we attempt to provide an overview of the COVID-19 vaccination landscape, review important concepts behind COVID-19 vaccinations, describe important vaccine reactions and assess their potential implications towards achieving herd immunity. As the title suggests, there are many open questions still to be answered. The certainty, urgency and importance of global herd immunity is, however, never in doubt.