Zoonotic viruses continually pose a pandemic threat. Infection of humans with viruses for which we typically have little or no prior immunity can result in epidemics with high morbidity and mortality. These epidemics can have public health and economic impact and can exacerbate civil unrest or political instability. Changes in human behavior in the past few decades-increased global travel, farming intensification, the exotic animal trade, and the impact of global warming on animal migratory patterns, habitats, and ecosystems-contribute to the increased frequency of cross-species transmission events. Investing in the pre-clinical advancement of vaccine candidates against diverse emerging viral threats is crucial for pandemic preparedness. Replication-defective adenoviral (Ad) vectors have demonstrated their utility as an outbreak-responsive vaccine platform during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Ad vectors are easy to engineer; are amenable to rapid, inexpensive manufacturing; are relatively safe and immunogenic in humans; and, importantly, do not require specialized cold-chain storage, making them an ideal platform for equitable global distribution or stockpiling. In this review, we discuss the progress in applying Ad-based vaccines against emerging viruses and summarize their global safety profile, as reflected by their widespread geographic use during the SARS-CoV-2 pandemic.