Orbitals which are extremely localized on molecular fragments represent a powerful tool for a number of purposes: just to cite a few examples, they allow to strongly reduce the complexity of calculations on large systems and they are easily transferable from one molecule to another one, providing a suitable and efficient way to build up the electronic structure of large molecules. Recently, we have developed efficient algorithms to determine Extremely Localized Molecular Orbitals (ELMOs) that will be reviewed in this paper. As a rigorous localization is strictly connected to a reduction in the number of variational parameters, which reflects into an increased value of the associated energy with respect to the Hartree Fock value, we have developed a number of strategies to relax the wavefunction built up using transferred localized orbitals. The extreme localization has also been exploited in connection with the 'Divide & Conquer' technique to determine large polypeptides electron densities assembled from orbitals computed on small model molecules. Moreover, we will discuss the recent application of the ELMOs in the framework of the hybrid QM/MM methods to describe the frontier region. We will also show that the ELMOs can be used to extract chemical interpretations from numerical results. A variety of applications will be presented. 2