Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel belonging to the large family of ABC exporters. The onset of the first experimental 3D structure, at atomic resolution, of a member of the ABC exporter family has permitted to perform homology modeling of the whole 3D structure (except for the regulatory R domain, which appears less structured). Presently, seven experimental structures of ABC exporters are known, in outward- and inward-facing conformations, having allowed to propose several models of the open and closed states of the ion channel, respectively. These models, together with the results coming from several molecular dynamics studies, have been widely used to better understand the molecular basis of the CFTR functions, which intimately depend on the intricate interactions between the different subunits. Recently, based on the improved knowledge we acquired from the experimental 3D structures, we made a new model of the open form of the CFTR channel, always based on the Sav1866 structure but refined in the Membrane Spanning Domains, which share very low levels of sequence identity with the ABC exporters templates. Moreover, we made a comprehensive analysis of the available 3D structures of ABC exporters, in order to define the conformational transition pathway followed between outward- and inward-facing conformations. This provide a new vision of the CFTR pore, both for the open and closed forms, the latter one being characterized by a more limited dissociation of the two Nucleotide-Binding Domains (NBDs) than for classical ABC transporters. Altogether, the whole set of models of the 3D structure of human CFTR in different conformations open the door to a search of specific molecules, which may be able to fix the assembly of the different domains of the protein, a major cause of the low ability of CFTR to reach and remain at the membrane.