C. elegans is an attractive model organism in biology, as it shows genetic similarity with humans, facilitates microscopic observation due to its transparency, and has a short life cycle. Moreover, many mutants expressing fluorescent proteins in particular cell types exist, and these can be advantageously used for gene/protein expression studies. Nematodes are traditionally cultured on agar plates seeded with E. coli bacteria as food and well plate-based worm cultures using liquid media have enabled high-throughput drug screening. In addition to the well plate format, microfluidics promises precise spatio-temporal handling and dosing of biological reagents for more controlled manipulation and culture of worms and embryos on-chip. I will first discuss reversible worm immobilization protocols, like the use of mechanical clamping or the temperature-sensitive sol-gel transition of a Pluronic solution, for high-resolution on-chip imaging. In particular, we exploited the imaging potential offered by microfluidic chips for performing fluorescent protein aggregation studies to characterize progress of neurodegenerative disease and for mitochondrial morphology studies. We have also implemented worm bio-communication assays on-chip, and have proposed microfluidic chips for automated embryo arraying, phenotyping, and long-term live imaging, as well as for drug studies performed during early embryogenesis. Microfluidic chips thereby allowed studying worm populations at individual animal resolution level and permitted investigating multiple phenotypes at different time points during worm development. Thereby we could observe individualized multi-phenotypic responses to drugs and genetic cues.