The role of practical clinical guidelines has been increasing over the last few years, and a progressive number of them have been published in mainstream medical journals. The issue of methodological quality of the guidelines, in the context, assumes major importance. We present what is considered to be the most advanced and reliable method of guideline development, through definition of the levels of scientific evidence upon which the grades of recommendations are constructed. As an example, we present a framework of evidence on therapy, diagnosis and prognosis. Finally, the four main principles referring to the translation of the results from the original studies into clinical recommendations are presented.