Macrocyclic hosts are the principal tools used in supramolecular chemistry because they can recognize other small molecules through non-covalent interactions. However, in terms of recognition ability, known macrocyclic hosts are often not comparable to bioreceptors. This may be due to the lack of functional groups inside the deep cavity, which is a common feature of bioreceptors. Most of the known macrocyclic hosts contain either a hydrophobic cavity or polar binding sites only. Macrocyclic hosts with functional groups inside a hydrophobic cavity are rare. In 2004, Glass and co-workers reported a pair of water-soluble naphthalene-based molecular tubes with amide protons in the well-defined deep cavity. The cavity feature is very similar to that of bioreceptors. However, the amide protons were not used in molecular recognition and were replaced in 2012 with allyl groups in order to improve the hydrophobic effect. We started our work on the basis of the Glass molecular tubes but paid close attention to the functional groups in the deep cavity. In this Account, we summarize our results on these biomimetic receptors, which we call naphthotubes. The inward-directed functional groups endow the corresponding naphthotubes with unique recognition abilities. Naphthotubes with hydrogen-bond acceptors (ether, ester, and imine) prefer to bind organic cations; naphthotubes with hydrogen-bond donors (urea, thiourea, and amide) can bind neutral molecules; amine naphthotubes are stimuli-responsive to acid/base. In particular, the water-soluble amide naphthotubes are able to selectively recognize highly hydrophilic molecules in water-a generally accepted challenge in supramolecular chemistry. The unique recognition ability of these naphthotubes provides the basis for their applications in sensing, self-assembly, and molecular machines. Fluorescent sensing of environmental contaminants in water, chiroptical sensing of small chiral molecules, allosteric cooperative self-assembly, dissipative self-assembly, and directional molecular shuttles have been demonstrated with these naphthotubes. Overall, we hope to convey the message that these naphthotubes have unique recognition properties and promising applications in diverse fields. We believe that further exploration of this class of macrocycles may lead to practical applications in, for example, biomedical science, environmental science, and other related fields.