The construction of supramolecular nanoscopic architectures has been intensively pursued because of their unique features for applications in nanoscience and biomimetic chemistry. Molecular self-assemblies of aromatic rod-coil amphiphiles consisting of rigid rod segments and hydrophilic flexible chains in aqueous solution provide a facile avenue into this area. This feature article highlights the recent progress regarding the construction of aqueous assemblies that result from the sophisticated design of aromatic rod-coils, with the aim to develop stimuli-responsive systems and bioactive materials. Important factors affecting the self-assembly morphologies are discussed and summarized. Dynamic structural changes triggered by temperature and guest molecules are demonstrated. Finally, the perspective of bioactive nanostructures originated from self-assembly of aromatic block amphiphiles is also introduced.