Due to the deeper penetration of near infrared (NIR) light and/or the strong absorption in the NIR range, NIR nanomaterials (NMs) have recently attracted great attention worldwide from the research community. Numerous and extensive studies have been devoted to the design, synthesis, and development of various NIR NMs for biomedical imaging and imaging-guided therapy of cancers, and the number of NIR NM-based papers has increased exponentially over the years. However, so far there is little information on the toxicological properties of NIR NMs and their long-term toxicity to human health. Moreover, most of the present data are conflicting and not generally available, hindering a proper evaluation of their effects on human health and the environment. Therefore, in this chapter, we focus primarily on the progress in toxicity studies of NIR NMs (including carbon-based materials, quantum dots, noble metal-based nanoparticles, upconversion nanoparticles, and narrow bandgap semiconductors) in the past several years. We discuss in detail how the biophysicochemical properties of NIR NMs influence their in vitro and in vivo toxicity, and finally present a broad overview of the available in vitro and in vivo toxicity assessments of NIR NMs.