Helical architectures including artwork and monuments, such us the Trajan’s column from Rome, were constructed as early as in the year 113 while the assemblies and the self-organizations of biological and synthetic macromolecules, only started to be discovered, elucidated and respectively designed during the early 1950s. This personalized account will first provide a historical journey starting from the Trajan’s column, that represents a classic mesoscopic helical architecture, to nanoscale biological macromolecules such as proteins, nucleic acids, carbohydrates and to supramolecular helical co-assemblies of proteins with nucleic acids, such as tobacco mosaic virus (TMV). It will continue with examples of synthetic helical covalent and supramolecular macromolecules. Their emerging functions ranging from mesoscopic scale to nanoscale and the current limitations of synthetic helical self-organizations will be discussed with selected examples mostly from the laboratory of the corresponding author.