Photodynamic therapy (PDT) is an innovative treatment where cancerous tumors are destroyed by the reactive oxygen species generated by photosensitizer drugs following activation with light typically of visible wavelengths. However, such visible light has limited penetration depth through skin and other healthy tissues, so deep-lying tumors can be difficult to treat. Upconversion nanoparticles (UCNPs) can be used as photosensitizer nanocarriers to overcome the limitation of visible light excitation. Near infrared (NIR) light has significantly deeper penetration depth than visible light through human tissue and can be used to excite the UCNPs that then emit light at shorter wavelengths. The emission of the UCNPs overlaps with the absorption band of the vast majority of currently used photosensitizers. Thus, the upconversion luminescence emitted by the UCNPs can be used to excite the photosensitizer bound in close proximity to the nanoparticles, inducing the generation of reactive oxygen species and thereby killing the cancer cells. This chapter introduces the proof of concept in the use of UCNPs for PDT and provides an insight into the state-of-art use of these nanomaterials for both in vitro and in vivo PDT.