Cation diffusion facilitator (CDF) proteins are a phylogenetically ubiquitous family of intermembrane transporters generally believed to play a role in the homeostasis of a wide range divalent metal cations. CDFs are found in a host of membranes, including the bacterial cell membrane, the vacuolar membrane of both plants and yeast, and the golgi apparatus of animals. As such, they are potentially useful in the engineering of hyperaccumulative phytoremediation systems. While not yet sufficient for reliable biotechnological manipulation, characterization of this family is proceeding briskly. Experimental data suggests that CDFs are generally homodimers that use proton antiport to drive substrate translocation across a membrane. This translocation of both substrate and protons is likely mediated by a combination of histidines, aspartates, and glutamates. Functional data has suggested that CDFs are not limited to metal homeostasis roles, as some appear to be determinants in the operation of high-volume metal resistance systems, and others may facilitate cation-donation as a means of signal transduction. This review seeks to give an overview of the data prompting these conclusions, while presenting additional data whose interpretation is still contentious.