Nanofluidics, the field interested in flows at the smallest scales, has grown at a fast pace, reaching an ever finer control of fluidic and ionic transport at the molecular level. Until now, artificial pores are far from reaching the wealth of functionalities of biological channels that regulate sensory detection, biological transport, and neurostransmission—all while operating at energies comparable to thermal noise. Here, we argue that artificial ionic machines can be designed by harnessing the entire wealth of phenomena available at the nanoscales and exploiting techniques developed in various fields of physics. As they are generally based on solid-state nanopores, rather than soft membranes and proteins, they should, in particular, aim at taking advantage of their specific properties, such as their electronic structure or their ability to interact with light. These observations call for the design of new ways of probing nanofluidic systems. Nanofluidics is now at the crossroads, there are new avenues to build complex ionic machines, and this may allow to develop new functionalities inspired by nature.