There are many therapies for the vaginismus type of genito-pelvic pain/penetration disorder. However, as frequently found when there are multiple treatments for a given pathological disorder, not any of them are highly effective for this problem. It has been hypothesized that increased tissue permeability may be the etiologic factor causing inflammation in various tissues leading to a variety of different pain syndromes in various organ systems, including, but not limited to, the pelvis. Treatment with dextroamphetamine sulfate has resulted in significant palliation of the pain in the majority of cases treated. The hypothesized mechanism is that this amphetamine releases dopamine from sympathetic nerve fibers, which, in turn, diminishes excessive infiltration of irritants, which are the etiologic factor for the pain. Ideally, the best proof of efficacy for the treatment of this type of vaginismus/dyspareunia syndrome by dextroamphetamine sulfate would be to conduct a randomized prospective double-blinded multi-center study. However, because of the generic status of this drug, it is highly unlikely that any pharmaceutical company would fund such a study. The most practical feasible method to determine efficacy would be to try the drug on a very convincing cases of long-term severe vaginismus/dyspareunia syndrome that failed to respond to standard therapy. Indeed, such a case was found in a 32-year-old woman whose vaginismus was detected at puberty, that was associated with severe dyspareunia 10 years later, so that neither insertion of tampons nor intercourse had been possible. Within one month of treatment her vulvodynia/dyspareunia were eradicated. The relief has persisted for three years. Hopefully this case report may encourage treating physicians who treat a lot of similar cases to evaluate a large series or conduct a randomized study comparing amphetamine therapy vs. their best treatment option to date.