Carboxylatopillar[n]arenes (CP[n]As, n = 5, 6, 7, 9, 10) are water soluble derivatives of pillar[n]arenes. The three-dimensional π-electron-rich cavity and carboxylate groups at the portals, enabled CP[n]A to have strong binding affinity in water, which has been successfully harnessed in fabricating responsive supramolecular assemblies from supra-amphiphiles and developing targeted drug delivery systems (DDSs). CP[n]A based supraamphiphiles have also been used for sensor applications. This review highlights the diverse applications of water soluble carboxylatopillar[n]arenes.