Premenstrual syndrome may be effective as an affirmative defense to a criminal charge if the defendant can show that (i) she was suffering from premenstrual syndrome at the time the crime was committed; and (ii) because of her condition, either that the criminal act was an involuntary act or that at the time of the criminal act she did not possess the mental state required by law for the commission of a crime. Premenstrual syndrome has been successfully pleaded as a criminal defense in Great Britain but has not been tested in American criminal courts. It may now be possible, however, because of the increase of behavioral, psychological, and physiological studies precisely characterizing premenstrual syndrome and elucidating the necessary criteria for its accurate diagnosis, for the appropriate defendant to assert this defense in an American court. This paper discusses (i) the use of recent scientific data to demonstrate the existence of premenstrual syndrome; (ii) the use of standardized psychological tests or physiological assays to demonstrate that the defendant suffers from premenstrual syndrome; and, (iii) the legal choices to be made and evidentiary hurdles that must be overcome in presenting a premenstrual syndrome defense.