In the lexicon of current medical practice, the term off–label is immediately understood through all levels of the profession. It refers to the use of a medication for a disease, or a dose, or method of administration that is not listed in the official labeling of its use. It is not only commonplace, but in some cases may represent the preferred therapy. On the other hand, the basis for off-label use may have the shakiest of support if using the evidence-based pyramid. Treatment is often based on anecdotes or small case series, although some therapies will have withstood the scrutiny of a randomized double-blind investigation. By its very nature though, off-label use represents extrapolation from prior experience and, more often than not, represents the early application of a yet-unproven therapy. It is important to note that this practice may not be inappropriate or ineffective, just unproven. The questions that naturally arise in this scenario span several areas, including concerns about safety, ethics, and responsibility.