The cystic fibrosis transmembrane conductance regulator (CFTR) regulates the flow of water and anions through the apical membrane of epithelia. CFTR, although functioning as an ion channel, is a member of the ATP binding cassette (ABC) transporter superfamily and shares a common mechanism with ABC transporters, in which conformational changes during gating are driven by ATP binding and hydrolysis. CFTR features a structural core common among ABC transporters: two transmembrane domains (TMDs) form the pore for anion flow, while two conserved nucleotide binding domains (NBDs) provide the binding sites for two ATP molecules. Mutations in CFTR affect the proper folding, trafficking and function of the protein, resulting in the genetic disease cystic fibrosis. The lack of experimental structures of the full length CFTR hampers a global understanding of CFTR mechanism, and thus the development of approaches directly targeting dysfunctional CFTR. In this study, we aimed at investigating possible conformational states visited by CFTR during the gating cycle. By means of homology modeling techniques, molecular models of CFTR were built using, as templates, the structures of four homologous ABC transporters, namely TM287-288, ABC-B10, McjD and Sav1866. Comparisons with published experimental data suggest that the TM287-288-based CFTR model could represent a closed-state channel, bearing a large opening between the intracellular sides of the TMDs while maintaining some contacts at the NBD interface. In this model the extracellular mouth of the pore is closed, not allowing passage of water molecules during simulations. In contrast, the McjD-based CFTR model, with tightly dimerized NBDs, provides features of an open-state channel, with openings on the upper TMDs that allow water to flow across the pore. Here, we present a detailed overview of the models, and discuss how they could help understand the role of specific residues in the gating cycle of CFTR, as well as the conformational transition from closed to open channels.