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The editorial staff and distinguished scientists in the field of cell signaling nominated diverse research as advances for 2013. Breakthroughs in understanding how spatial and temporal signals control cellular behavior ranged from filtering high-frequency stimuli to interpreting circadian inputs. This year’s nominations also highlight the importance of understanding cell signaling in the context of physiology and disease, such as links between the nervous system and cancer. Furthermore, the application of new techniques to study cell signaling—such as optogenetics, DNA editing with CRISPR-Cas9, and sequencing untranslated regions of transcripts—continues to expand the realm and impact of signaling research.