An internal time-keeping mechanism has been observed in almost every organism studied from archaea to humans. This circadian clock provides a competitive advantage in fitness and survival ( 18, 30, 95, 129, 137 ). Researchers have uncovered the molecular composition of this internal clock by combining enzymology, molecular biology, genetics, and modeling approaches. However, understanding the mechanistic link between the clock and output responses has been elusive. In three model organisms, Arabidopsis thaliana, Drosophila melanogaster, and Mus musculus, whole-genome expression arrays have enabled researchers to investigate how maintaining a time-keeping mechanism connects to an adaptive advantage. Here, we review the impacts transcriptomics have had on our understanding of the clock and how this molecular clock connects with system-level circadian responses. We explore the discoveries made possible by high-throughput RNA assays, the network approaches used to investigate these large transcript datasets, and potential future directions.