All enveloped viruses initiate infection by attaching to host cells followed by membrane fusion via interaction between viral surface proteins and receptor/co-receptor molecules on target cells, and this interaction is often a key determinant controlling viral tissue tropism and/or host range. As described above, it has been demonstrated that filoviruses utilize multiple molecules for their entry into cells. However, it remains elusive whether these molecules serve as functional receptors mediating both viral attachment and membrane fusion or play independent roles as either attachment receptors or fusion receptors. More importantly, none of the cellular molecules identified so far explains filovirus tissue tropism and host range reasonably. It might also be hypothesized that filoviruses do not use a single common receptor to infect a broad range of cells and, unlike many other viruses, may not need a "specific" receptor. Although the overall tropism and pathogenicity of filoviruses is controlled by multiple host cell factors (e.g., interactions with the host immune system), further studies aimed at identification of cellular molecules interacting with GP are needed to fully understand the mechanisms of cellular entry of filoviruses, and may shed light on the development of strategies for prophylaxis and treatment of Marburg and Ebola hemorrhagic fevers.