Cellulose nanocrystals (CNCs) are a biobased nanomaterial attracting increasing interest for a range of potential applications. This article reviews the current literature on the pulmonary, oral, dermal, and cytotoxicity of CNCs. Current studies of the oral and dermal toxicity of CNCs have shown a lack of adverse health effects, whereas studies of the pulmonary and cytotoxicity have yielded discordant results. Additional studies are needed to support the general conclusion that CNCs are nontoxic on ingestion or contact with the skin and to determine whether CNCs have adverse health effects on inhalation or elicit inflammatory or oxidative stress responses at the cellular level. This review underscores the importance of careful sample characterization and exclusion of interfering factors, such as the presence of endotoxins or toxic chemical impurities, for a detailed understanding of the potential adverse health effects of CNCs by various exposure routes.