Vaccine marketing authorization holders (MAHs) are responsible for the conduction of global vaccine pharmacovigilance on their vaccine products. A safety signal is detected when a new adverse event (AE) or aspect of an AE occurs after exposure to the vaccine and warrants further investigation to determine whether a causal association may exist. Signal detection and evaluation (signal management) begins at the start of vaccine development, before an MAH submits an application for authorization to regulatory authorities, continues through the course of all clinical trials, and carries on beyond development into the post-marketing phase. As long as the vaccine remains authorized anywhere in the world, pharmacovigilance continues. During the time that the COVID-19 vaccine became widely available after authorization and approval, clinical trials were also ongoing, and therefore all clinical development and post-authorization safety information was closely monitored for safety by the MAH. MAH pharmacovigilance activities were adapted to manage the unprecedented volume of safety information that became available within a very short timeframe following worldwide vaccination campaigns. No vaccine had previously been administered to such a large number of individuals in such a short time, nor had there previously been a public health vaccine experience that was the subject of so many medical and non-medical writings. The MAH's COVID-19 vaccine signal detection methods included the continuous review of accruing clinical trial data and the quantitative and qualitative analyses of spontaneously reported experiences. Review of published and unpublished medical literature and epidemiology-based analyses such as observed vs. expected analysis based on reported adverse events following immunization (AEFIs) played key roles in pharmacovigilance and signal management. All methods of signal detection and evaluation have caveats, but when considered in totality, can advance our understanding of a vaccine's safety profile and therefore the risk-benefit considerations for vaccinating both individuals and large populations of people. All COVID-19 vaccines authorized for use were subject to an unprecedented level of pharmacovigilance by their individual MAHs, national regulatory authorities, public health organizations, and others during the years immediately following regulatory authorization and full approval. The intense worldwide focus on pharmacovigilance and the need for MAHs and regulatory/health authorities to quickly evaluate incoming safety information, spurred frequent and timely communications between national and regional health authorities and between MAHs and regulatory/health authorities, spotlighting a unique opportunity for individuals committed to patient safety to share important accruing safety information in a collegial and less traditionally formal manner than usual. The global pandemic precipitated by the SARS-CoV-2 virus created a significant impetus for MAHs to develop innovative vaccines to change the course of the COVID-19 pandemic. Pharmacovigilance also had to meet unprecedented needs. In this article, unique aspects of COVID-19 vaccine pharmacovigilance encountered by one MAH will be summarized.