We explore the relationship between satellite retrievals of aerosol optical depth (AOD) and surface aerosol mass concentrations over a subtropical urban area, namely, Santiago, Chile (33.5°S, 70.6°W, 500 m.a.s.l.). We compare 11 years of AOD from the MODerate resolution Imaging Spectroradiometer (MODIS) with in situ particulate matter mass concentrations (PM). MODIS AOD reaches its maximum in summer and minimum in winter, the opposite of the annual cycle of surface PM. To improve our understanding of the relevant governing processes, we use a simple model that estimates the boundary layer (BL) AOD based on measured PM, relative humidity and BL height (BLH) as well as best estimates of aerosol composition, size distribution, and optical properties. Model results indicate that a weak annual AOD cycle is due to the opposite annual cycles in BLH and PM, which is largely supported by the Aerosol Robotic NETwork (AERONET) data collected in 2001 and 2002 in Santiago. We identify a possible bias linked to the operational estimate of surface reflectance that may lead to a spurious summer maximum in MODIS AOD over Santiago. This misfit in surface reflectance appears to affect not only Santiago but also a significant area of the semi-arid Southern South America. Sensitivity experiments with the simple model indicate an underestimate of simulated AOD as compared to AERONET data. This underestimate points to the possible role of residual aerosol layers in the AOD measured at the surface (not included in the simple model). Cirrus clouds appear not to play a significant role in explaining the MODIS AOD seasonality. The need for improved characterizations of aerosol properties and their temporal and spatial distribution in cities such as Santiago is emphasized.