The ultimate goal in protein design is to elucidate the fundamental principles that determine structure. With increased understanding of the molecular basis underlying the sequence-structure relationship may come the ability to control it and, thereby, to generate proteins with desired specifications. Channel proteins, which mediate cell signaling, are ideally suitable for protein design. Plausible molecular blueprints for the pore-forming structure are bundles of amphipathic alpha-helices or beta-barrels that cluster together to generate a hydrophilic channel. This review focuses on the progress achieved to produce such designs and on the approximation of the synthetic channels to the targeted biological function.