Remarkably, protein channels transporting polar substances such as water, protons, and ions are often lined by predominantly non-polar residues. The unique structural, dynamic, and thermodynamic properties of water and ions in molecular confinement help explain this puzzling observation. Computer simulations of solvated nanotubes and proteins show that weakly polar cavities can be filled by water at equilibrium, but such filling is highly sensitive to small variations in the polarity of the cavity. In the filled state, water forms wires and clusters held together by tight hydrogen bonds. Simulations on quantum energy surfaces also show that 1D water wires in hydrophobic environments facilitate rapid proton motion. The unique properties of water in weakly polar channels help explain the rapid flow of water through molecular pores, the controlled proton flow in enzymes, the gating of ion transport through membrane channels, and the function of mitochondrial proton pumps.