Red Desert, though it is often appended to the “trilogy” that preceded it (perhaps because it once again stars Monica Vitti and seems to deal with alienation), in fact represents an important turning point in Antonioni's work, one that the director himself clearly recognized. Speaking to Godard in a celebrated interview conducted in 1964, Antonioni said: “This time, I haven't made a film about feelings. The results that I had obtained from my previous films – good or bad as they may be – have by now become obsolete. The focus is on something completely different” (p. 287; translation modified). He continued: “At one time, I was interested in the relationships of characters to one another. Now, instead, the main character must confront her social environment, and that's why I treat the story in a completely different way” (p. 287).

Red Desert was to be the last film in which a woman appears as the central protagonist, and it was to be Antonioni's last Italian film, strictly speaking, as well. Many critics have in addition detected in this film a major shift in the director's approach to central epistemological and moral questions such as the nature of vision and our relation to reality.