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Human adenovirus (HAdV) is a very common pathogen that typically causes minor disease in most patients. However, the virus can cause significant morbidity and mortality in certain populations, including young children, the elderly, and those with compromised immune systems. Currently, there are no approved therapeutics to treat HAdV infections, and the standard treatment relies on drugs approved to combat other viral infections. Such treatments often show inconsistent efficacy, and therefore, more effective antiviral therapies are necessary. In this review, we discuss recent developments in the search for new chemical and biological anti-HAdV therapeutics, including drugs that are currently undergoing preclinical/clinical testing, and small molecule screens for the identification of novel compounds that abrogate HAdV replication and disease.