Stem cells exhibit promise in numerous areas of regenerative medicine. Their fate and function are governed by a combination of intrinsic determinants and signals from the local microenvironment, or niche. An understanding of the mechanisms underlying both embryonic and adult stem cell functions has been greatly enhanced by the recent development of several high-throughput technologies: microfabricated platforms, including cellular microarrays, to investigate the combinatorial effects of microenvironmental stimuli and large-scale screens utilizing small molecules and short interfering RNAs to identify crucial genetic and signaling elements. Furthermore, the integration of these systems with other versatile platforms, such as microfluidics and lentiviral microarrays, will continue to enable the detailed elucidation of stem cell processes, and thus, greatly contribute to the development of stem cell based therapies.