Compound screening is a powerful tool to identify new therapeutic targets, drug leads, and elucidate the fundamental mechanisms of biological processes. We report here the results of the first in vivo small-molecule screens for compounds enhancing neuronal regeneration. These screens are enabled by the microfluidic devices we have developed for C. elegans. The devices enable rapid and repeatable animal immobilization which allows high-throughput and precise surgery. Following surgery, animals are exposed to the contents of a small-molecule library and assayed for neuronal regeneration. Using this screening method we have identified several compounds that enhance neural regeneration in vivo.