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Spitzer provides substantial advances for studies of external galaxies: 1.) it has the very high sensitivity toward extended, low‐surface‐brightness sources made possible by a cryogenic telescope in space; 2.) the use of large format arrays and projected pixel scales that sample the telescope image well provide substantial improvements in angular resolution compared with previous space infrared telescopes; and 3.) its spectrograph has wavelength resolution well‐suited to extragalactic studies, as well as high performance arrays that provide a major advance in sensitivity. We show how these capabilities are already leading to new possibilities in studying the structure of nearby galaxies. Combined with recent breakthroughs in high quality imaging at other wavelengths, we can anticipate a substantial improvement in our understanding of how different components of a galaxy relate to each other and how their interactions influence galaxy evolution. In addition, Spitzer is advancing our understanding of the behavior of the polyaromatic hydrocarbon (PAH) emission features, as a function of environment and metallicity. New features are also being discovered due to the high‐sensitivity mapping capabilities of the spectrograph. An additional direction for research with Spitzer arises from its deep survey capabilities and the possibility of testing how the spectral energy distributions of galaxies evolve at large look‐back times.