Main TextA megacity typically refers to a metropolitan area with more than 10 million people. The number of megacities worldwide has increased from 8 in 1970 to 34 in 2016 with their total population exceeding 650 million (City Population, 2016). Air pollution, a consequence of increased population and urbanisation, is a common concern in megacities. Here we focus on the Metropolitan Area of São Paulo (MASP), which is the 5 th most populous urban region in the world and the second most populated region in Latin America (UN, 2014), making up ~10% of the total population of Brazil. With 21 million inhabitants and 8511 km 2 area (Fig. 1a), the MASP includes 38 metropolitan areas surrounding the city of São Paulo that has a population of 12 million (IBGE, 2016). What makes São Paulo distinctly different from all other megacities in the world is that its vehicle fleet operates exclusively on biofuel blends (sugarcane ethanol and soya diesel) in diesel, making it a unique biofuel-driven megacity. Yet, São Paulo's air quality face challenges to meet its national standards, which are relatively relaxed compared with the megacities of Asia (e.g., Delhi) or Europe (e.g., London). While the events of highly elevated concentrations of particulate matter (PM) are similarly common as in other megacities, the underlining factors responsible for them are unique to São Paulo and the questions are: (i) how can the air quality be improved considering that numerous interventions have already been taken in controlling emissions from vehicular fleet? (ii) how can the transportation system be transformed to make it emission-neutral? (iii) how the emissions from the main emitters such as the diesel trucks and buses can be reduced? and (iv) how the changes in the content of biofuel in diesel have influenced the exceedances and ozone formation? The aim of this paper is to propose answers to the above questions in the context of distinctness in the vehicle fleet, hitherto overlooked sources, underlining causes for pollution exceedances, and to suggest future directions and research needs to better understand and manage air quality of this unique megacity.Unique vehicle fleet and fuels it operates on: The MASP includes more than 7 million of road vehicles, with an average of 0.34 vehicles per inhabitant (CETESB, 2015). Light duty vehicles (LDVs), including private cars and taxis, dominate the traffic fleet with 85% share, followed by motorcycles (12%) and heavy duty vehicles (HDVs; 3%) (CETESB, 2013). The fleet of LDV, HDV and motorcycle have increased by 12.7, 10 and 9.6% between 2009 and 2012, respectively. The proportion of flexfuel vehicles that can run on ethanol or gasohol (gasoline with 25-27% ethanol) is increasing in MASP every day as 94% of vehicles sold in 2013 were flex-fuel (Posada and Façanha, 2015). Currently, the proportion of gasohol-driven LDVs is 55%, followed by flex-fuel vehicles (38%), ethanol (4%) and diesel (2%) (CETESB, 2012). To enable comparison, the relevant characteristics of the five world's largest megacitie...