The involvement of the metallic element iron in various biological systems is well known. In many cases, iron is employed in the form of a heme group and the family of proteins and catalytic enzymes that contain heme is well documented (e.g. the globins, cytochromes, and P450s). For many of these proteins, there is a great deal of information available in terms of structures, catalytic mechanism and function. This has led to a collective view that the main role of heme in biological systems is as a prosthetic group, binding to individual proteins and thereby conferring upon them particular functional properties. It is now becoming clear that this description represents only a part of a much more complex involvement of heme in biology and that other roles, for example in regulation and sensing, have been overlooked. This mini-review focuses on one such emerging role: the regulatory role of heme in neurons.