Rare earth ions doped nanomaterials have excellent photon upconversion property, showing great promise in broad frontier applications like nanophotonics, bioimaging-guided therapy and life science. Unlike conventional luminescence, the orthogonal upconversion is a newly observed phenomenon in rare earth luminescent nanomaterials, which is able to yield different emission colors by altering the excitation conditions. This allows for the construction of nano-platform, which is significant for the relevant frontier applications. This review summarizes the latest research progresses of orthogonal luminescence of rare earth ions, and presents a thorough discussion on the core-shell structure design principles and its key role in spectral manipulation towards orthogonal emission as well as its various applications including full-color display, optical memory, anti-counterfeiting security and bioimaging-guided therapy. The limitations of orthogonal luminescence are commented and future development are also prospected.