Nanochannels offer significant practical advantages in many fields due to their interesting characteristics, such as flexibility in shape and size, robustness, low-cost and their ability to be modified based on the required applications. The effectiveness of ion separation in nanochannels can be assessed based on the selective transport of the desired ions and the rate of the transportation process. This paper aims to provide an extensive review of ion-based nanochannels, including their working principles and ion-selective behaviors. Nanochannel fabrication strategies and their applications are discussed. Key nanochannel design factors and their roles in governing ion-selective transport are also reviewed. The contribution of size, charge, wettability, and recognition ability of the nanochannels on the selectivity mechanisms are discussed. Specific consideration is made to nanochannel applications in sensing and biosensing assays. Finally, an attempt is made to address the commercial implementation and future outlook of the nanochannels to guide researchers in emerging avenues of research. © 2021 Wiley-VCH GmbH