Weighted genotypic resistance scores represent a step towards excellence in the interpretation of HIV type-1 (HIV-1) resistance to antiretroviral drugs. They can predict phenotypic resistance and clinical response better than any other unweighted score. With the addition of mutations associated with an increased response and the refinement of the initial weighted score in a different dataset of individuals, the updated tipranavir score will doubtlessly be a thorough and user-friendly tool that narrows the gap existing between basic science in HIV-1 resistance to antiretrovirals and daily point-of-care clinical practice. The accuracy of the design and the steps used in its validation represent a milestone in HIV-1 resistance knowledge that should also be applied to other antiretroviral drugs in the future.