The permeation of charged organic molecules through membranes is not fully understood. Of particular importance is permeation through membranes that have a voltage maintained across them. For example, the membrane potential across the plasma membrane of animal cells is 30-60 mV, while those across mitochondrial inner membranes and plant cells are two- to three-fold higher. Of critical importance to the effect of permeation is whether an ion crosses a membrane alone or with its counterion because an ion that crosses alone may accumulate on one side of the membrane in accordance with Nernst equation and may carry a current. We will explore the factors governing the barrier to ion translocation in studies that encompass synthesis of different types of organic ions, testing with black lipid membrane experiments, computational studies, and applications to drug delivery, to devices and sensors.