Influenza A viruses (IAVs) pose a major public health threat worldwide. Recent experience with the 2013 H7N9 outbreak in China and the 2009 "swine flu" pandemic have shown that antiviral vaccines and drugs fall short of controlling the spread of disease in a timely and effective manner. Major problems include rapid emergence of drug-resistant influenza virus strains and the slow process of vaccine production. With the threat of a highly pathogenic H5N1 bird-flu pandemic looming large, it is crucial to develop novel ways of combating influenza A viruses. Targeting the host factors critical for influenza A virus replication has shown promise as a strategy to develop novel antiviral molecules with broad-spectrum protection. In this review, we summarize the role of currently identified host factors that play a critical role in the influenza A virus life cycle and discuss the most promising candidates for anti-influenza therapeutics.