The rapid development and production of nanomaterials has created some concerns about their potential hazard on the environment,human health and safety.However,since the list of materials that may generate such concerns is very long,it is impossible to test them all.It is therefore usually recommended to use some small compositional nanomaterial libraries to perform initial toxicity screening,based on which combinatorial libraries are then introduced for more in-depth studies.All nanomaterials in the compositional and combinatorial libraries must be rigorously characterized before any biological studies.In this review,several major categories of physicochemical properties that must be characterized are discussed,along with different analytical techniques that are commonly used.Some case studies from the University of California Center for Environmental Implications of Nanotechnology are also chosen to demonstrate the effective use of compositional and combinatorial nanomaterials libraries to identify the role of some key physicochemical properties and to establish true quantitative structure–activity relationships.Examples on how to use the knowledge generated from those studies to design safer nanomaterials for improved biological applications are also presented.