Metal nanoclusters (NCs), typically consisting of a few to tens of metal atoms, bridge the gap between organometallic compounds and crystalline metal nanoparticles. As their size approaches the Fermi wavelength of electrons, metal NCs exhibit discrete energy levels, which in turn result in the emergence of intriguing physical and chemical (or physicochemical) properties, especially strong fluorescence. Compared with noble metals, copper is a relatively earth-abundant and cost-effective metal. Theoretical and experimental studies have shown that copper NCs (CuNCs) possess unique photoluminescent properties. To highlight these achievements, this review begins by providing an overview of a multitude of factors that play central roles in the fluorescence of CuNCs. Additionally, a critical perspective of how the aggregation of CuNCs can efficiently improve the florescent stability, tunability and intensity is also discussed. Following, we present representative applications of CuNCs in detection and in-vivo/in-vitro imaging and point out that in-situ generation of CuNCs for sensing and bioimaging may be an entry point for the in-depth studies of CuNCs as an intriguing probe. Finally, we outline current challenges and our perspective on the development of CuNCs.