The regional boundaries of the Sonoran Desert were first described by John Harshberger in 1911 and refined by Forrest Shreve in the 1940s on the basis of the desert’s unique vegetation and flora. It is roughly divided by the U.S./Mexico international boundary with about 60 percent in Mexico. The present cultural landscape of the Sonoran Desert is an expression of its historically diverse cultures and their uses of available water and desert plants. The Indians, who had depended totally on local resources for their sustenance, were forced to accept the limitations of scarce water, whereas modern-day Mexican and American societies rely on technologies that allow them to import almost all that they need to live in the desert, including water. Five selected vignettes illustrate the salient features concerning changing human perceptions and uses of the desert’s water and plant resources as they relate to the development of the modern landscape. These vignettes elucidate the cultural roots of the landscape and its distinctiveness.