One of the challenges for therapeutic clinical trials in FRDA is the development of outcome measures, which should have good reliability, validity, reproducibility and sensitivity to change. Nowadays, more than in the past, the longitudinal studies of FRDA disease are important to analyze disease progression and to improve the accuracy of prognosis but mostly to prove the adequacy and the sensitivity to change of the outcome measures. An accurate knowledge of the disease natural history is in fact a critical assumption upon which a clinical trial has to be designed.