The study of small-size animal models, such as the roundworm C. elegans, has provided great insight into several in vivo biological processes, extending from cell apoptosis to neural network computing. The physical manipulation of this micron-sized worm has always been a challenging task. Here, we discuss the applications, capabilities and future directions of a new family of worm manipulation tools, the 'worm chips'. Worm chips are microfabricated devices capable of precisely manipulating single worms or a population of worms and their environment. Worm chips pose a paradigm shift in current methodologies as they are capable of handling live worms in an automated fashion, opening up a new direction in in vivo small-size organism studies.