Air quality in the world’s most populous cities (megacities) impacts a sizeable proportion of the global population. Projected population increases in urban areas over the coming decades underscore the importance of understanding the sources, variations, and impacts of air pollution. While some megacities experience episodic extreme events, in others, extremely degraded air quality is chronic. In this review, we assess recent findings on the impacts of extreme air pollution, which we define as concentrations exceeding international guidelines. We highlight recent research on pollution and growth trends in the most populous megacities. We then emphasize important new methods for monitoring air pollution exposure, such as satellite-based estimates, and suggest future needs, including a more comprehensive understanding of the health and economic impacts. The primary conclusion to emerge is that, globally, while the extreme air pollution burden is highest in megacities in developing countries, significant gaps remain in our understanding.