The pH regulation of transmembrane ion transport is critical for biological processes and has a direct implication on diseases such as cancer. Synthetic transporters that can be regulated using pH show promise as therapeutic agents. This review highlights the importance of the fundamental principles of acid-base chemistry in achieving pH regulation. A systematic classification of transporters based on the pKa of their pH-responsive units aids in correlating the pH regulation of ion transport with the molecular structure. This review also summarises the applications of these transporters and their efficacy in cancer therapy.