Zinc oxide (ZnO), a direct, wide band gap and n-type metal oxide semiconductor, is being anticipated as the next generation functional nano-material towards remarkably diversified sensing applications. ZnO and its composites have revealed a new era in the fabrication of sensors owing to their excellent opto-electronic, physicochemical, electrical properties such as low dielectric constant, plentiful Zn-O bonds, high luminous transmittance, good physicochemical stability, huge excitation binding energy, non-toxicity, biocompatibility, large surface area to volume ratio and so on. This comprehensive review summarizes the applications of ZnO nano-structures in the areas of environmental monitoring, biomedical, and optical sensing. Fundamental sensing mechanisms of the ZnO based sensors are examined to provide a better insight into the role of ZnO in each of these sensors. Wherever relevant, limitations of the existing approaches and future outlook have also been discussed. © 2022