We are at a critical stage in the COVID-19 pandemic where vaccinations are being rolled out globally, in a race against time to get ahead of the SARS-CoV-2 coronavirus and the emergence of more highly transmissible variants. A range of vaccines have been created and received either emergency approval or full licensure. To attain the upper hand, maximum vaccine synthesis, deployment and uptake as rapidly as possible is essential. However, vaccine uptake, particularly in younger adults is dropping, at least in part fuelled by reports of rare complications associated with specific vaccines. This review considers how vaccination with adenovirus vector-based vaccines against the SARS-CoV-2 coronavirus might cause rare cases of thrombosis and thrombocytopenia in some recipients. A thorough understanding of the underlying cellular and molecular mechanisms that mediate this syndrome may help to identify methods to prevent these very rare, but serious side-effects. This will also help facilitate the identification of those at highest risk from these outcomes, so that we can work towards a stratified approach to vaccine deployment to mitigate these risks.