The Spitzer Space Telescope has delivered impressive infrared images of numerous low-mass star forming regions at unprecedented sensitivity. In this paper we focus on their high-mass counterparts, the most massive HII regions in the Local Group: NGC3603 (MW), W49A (MW), 30 Doradus (LMC), NGC346 (SMC), and NGC604 (M33). The deep mid-IR images, taken with IRAC show the complex structure of the ISM, the interplay between ISM and stellar clusters, and reveal new sites of star formation. We compare the IRAC data with observations from Chandra and find good anti-correlations between the mid-IR and soft X-ray emission regions. We also investigate the commonalities and differences between the giant HII regions NGC604 and 30 Doradus.