The Nrf2 transcription factor belongs to the Cap’n’collar family, named after the founding member of this group, the product of the Drosophila cap’n’collar gene. The encoded protein, Cap’n’collar, abbreviated Cnc, offers a convenient and accessible model to study the structure, function and biology of Nrf2 transcription factors at organism, tissue, cell and molecular levels, using the powerful genetic, genomic and biochemical tools available in Drosophila. In this review we provide an account of the original identification of Cnc as a regulator of embryonic development. We will then describe the discovery of Nrf2 like-functions of Cnc and its role in acute stress signaling and aging. The establishment of Drosophila as a model organism in which the mechanisms and functions of Nrf2 signaling can be studied has led to several discoveries, the regulation of stem cell activity by an Nrf2-mediated redox mechanism, the interaction of Nrf2 with p62 and Myc in the control of tissue growth and unfolded protein response, and more. Several of these more recent lines of investigation will be highlighted. Model organisms like fly and worm remain powerful experimental platforms that can help to unravel the many remaining puzzles regarding the role of Nrf2 and its relatives in controlling the physiology and maintaining the health of multicellular organisms.