Human Adenoviruses (HAdV) are large non-enveloped viruses containing a linear, double-stranded DNA genome with 80-100nm in size surrounded by an icosahedral capsid with type-specific antigens. HAdV are the causative agent for lytic and persistant infections, associated with clinical symptoms such as gastroenteritis, keratoconjunvtivitis, pneumonia, hepatitis and encephalitis. These viruses are non-pathogenic for healthy individuals due to protective immunity. In the absence of protective immunity, e.g. in allogeneic bone marrow transplant patients, HAdV infections can become lethal. Alarmingly, since 2011 various outbreaks of highly pathogenic, pneumotropic HAd types were reported in China, the United States, Canada and Ireland causing severe and lethal cases of respiratory diseases in immunocompetent patients. However, until today there is no effective chemotherapeutic drug available to treat HAdV infections. Commonly used antiviral treatment such as cidovovir and ribavirin only limit HAdV but cannot cure severe infection and rescue the patient. Due to these facts, there is an urgent need to understand virus/host cooperations at very early steps during infection to develop novel inhibitors against specific targets to efficiently prevent HAdV-mediated diseases and mortality of patients.