Over the past few years, engineered nanomaterials (ENMs) have penetrated nearly every sector of modern life and their broad-scale use is steadily and rapidly increasing. The (expected) elevated levels of ENMs in the environment raise concerns with regard to their potential environmental impact, but environmental risk assessment of released ENMs lags behind invention and today's global consumption volumes. Although considerable progress has been achieved in understanding particle behavior in complex systems and numerous studies have investigated the environmental hazards of ENMs in recent years, the link between these two aspects is less developed. This review provides an overview of what is known about ENMs in freshwater systems and explores the applicability of the bioavailability concept known from aquatic trace metal toxicology. The concept of bioavailability may provide a useful framework to link the “chemical and physical speciation” of ENMs with their possible biological effects but likely requires some ENM specific adaptations. However, there are still considerable knowledge gaps with respect to ENM “speciation” in natural aquatic systems and it remains unclear if it is realistic (by analogy to free metal ions) to search for a specific ENM form that could be used as a measure of biological reactivity. Major knowledge gaps concern the effects of agglomeration on bioavailability, cellular internalization routes, intracellular compartmentalization as well as dissolved organic matter– protein competition on the surface of internalized ENPs.