© 2018, Springer Nature Limited.The conversion of low-energy light into high-energy light, also known as upconversion, can be exploited in life science applications such as bioimaging and phototherapy. Sensitized triplet–triplet annihilation upconversion (sTTA-UC) is one type of upconversion in which a photosensitizer is excited using a low-energy light and then transfers energy to an annihilator that emits at much higher energy. Changing the molecular components enables the fine-tuning of excitation and emission wavelengths. sTTA-UC is an appealing approach because it results in high upconversion efficiencies. However, its sensitivity to the presence of dioxygen in living cells and biological tissues is problematic. In this Review, the essential requirements of sTTA-UC for bio-nanodevices and life science applications are outlined before discussing the different ways to circumvent the dioxygen sensitivity of sTTA-UC.