Grouping of similar nanoparticles allowing read-across to fill toxicological data gaps is a potentially rapid and low-cost solution to provide more information about hazard. Read-across for nanoparticles can learn much from the experience gained from preparing read-across arguments for small molecules. This chapter describes some of the wisdom in applying read-across for small molecules and shows how this may be applied to filling data gaps regarding nanoparticles. Globally there are many legislative frameworks for the regulation of chemicals that have promoted the use of read-across for toxicity prediction. Read-across, in particular, will optimize limited resources and provide information regarding hazard related to classes of nanoparticles that are being expanded or created. The developer of a read-across for nanoparticles should have knowledge of the available databases and computational tools and be able to use them proficiently, being able to understand the output. Assessing the confidence of any prediction, and especially that based on read-across, is often a subjective process.