Technical Abstract: Background. Shewanella oneidensis is a target of extensive research efforts in the fields of bioelectrochemical systems and bioremediation because of its versatile metabolic capabilities, especially in regards to the respiration with extracellular electron acceptors. Here, we took a global approach to evaluate physiological activity with an electrode as electron acceptor for the generation of electric current. We performed expression analysis with deoxyribonucleic acid (DNA) microarrays to compare the overall gene expression with an electrode to that with soluble iron (III) or oxygen as the electron acceptor. Results. We confirmed the differential expression of many genes that have previously been reported to be involved in electrode respiration, such as the entire mtr operon. We also formulate hypotheses on other possible gene involvements in electrode respiration: i) the role of ScyA in inter-protein electron transfer; ii) an electron transfer pathway through the dimethyl sulfoxide (DSMO) reductase proteins that dissipates electrons away from the mtr pathway; and iii) a regulatory role of the cbb3-type cytochrome c oxidase under anaerobic conditions. Further, we hypothesize that the electrode respiration imposes a significant stress on the microorganisms, resulting in higher energetic costs for electrode respiration than for soluble iron (III) respiration, which fosters a higher metabolic turnover to cover energy needs. Conclusions. Our gene expression analyses gave insight into the physiological state of S. oneidensis when grown with an electrode as electron acceptor. Besides the confirmation of predicted gene functions, we developed hypotheses for several previously unknown gene functions and for a possible stress situation for S. oneidensis during electrode respiration. Our hypotheses now require experimental verification.