The field of Duchenne muscular dystrophy has dramatically changed in the last few decades. With the introduction of non invasive ventilation there has been a marked increase in survival and the overall improvements in standards of care, including the advent of steroids as part of routine practice, have produced a significant improvement of the disease course with slowing down of the deterioration. Over the last two decades there has also been a better understanding of the mechanisms underlying the disease with a number of therapeutical approaches targeting different steps of this mechanism, from fene therapy, addressing the root problem of the disease, to approaches also targeting dystrophin restoration through exon skipping or other mRNA approaches, or directly targeting the muscle by reducing fibrosis or inflammation. The advent of these approaches and of the first clinical trials has highlighted the need for natural history studies to better understand the variability of the progression in relation to age, functional status and to a number of other variables including type and site of mutation or possible genetic modifiers. Special attention has recently been paid to the possibility to identify trajectories of progression or prognostic factors by using statistical and machine learning models that could help to define individual trajectories, also in response to treatment.