Molecular electronics originally promised miniaturization of molecular devices using Nature’s smallest building blocks to allow for novel electronic function by simply altering the chemical structure of the molecular component. Molecular electronics has evolved towards a complementary technology to silicon-based electronics, providing functionalities not possible with classical electronic devices. After more than 40 years of experiments, it remains a challenge to rationally design molecule-electrode junctions due the complex interplay between electronic structure and the chemical/supramolecular arrangement of the interfaces. Unlike traditional CMOS electronics, comprehensive design rules for molecular junctions are not available yet. Only bits and pieces have been published scattered across disciplines, including interface engineering, supramolecular chemistry, surface science, computational science, physics, chemistry, optics, biology and micro/nanofabrication.