The rapid accumulation of fully sequenced prokaryotic genomes provides unprecedented information for biological studies of bacterial and archaeal organisms in a systematic manner. Operons are the basic functional units for conducting such studies. Here, we review an operon database DOOR (the Database of prOkaryotic OpeRons) that we have previously developed and continue to update. Currently, the database contains 6xe2x80x89975xe2x80x89454 computationally predicted operons in 2072 complete genomes. In addition, the database also contains the following information: (i) transcriptional units for 24 genomes derived using publicly available transcriptomic data, (ii) orthologous gene mapping across genomes, (iii) 6408 cis-regulatory motifs for transcriptional factors of some operons for 203 genomes, (iv) 3xe2x80x89456xe2x80x89718 Rho-independent terminators for 2072 genomes, as well as (v) a suite of tools in support of applications of the predicted operons. In this review, we will explain how such data are computationally derived and demonstrate how they can be used to derive a wide range of higher-level information needed for systems biology studies to tackle complex and fundamental biology questions.