Viruses are obligate, intracellular parasites that depend on host cells for successful propagation. Upon infection of host cells, positivestrand RNA viruses exploit and hijack cellular machinery and reprogram these cells into viral "factories" through various protein-protein, protein- RNA, and protein-lipid interactions. The molecular interplay between host factors and invading viruses is a continuous process throughout the entire viral life cycle and determines virus host range and viral pathogenesis, as well as driving viral evolution. Studies of host factors have contributed insights into their normal cellular functions and helped identify attractive targets for antiviral drug development. With the development of high throughput screening, functional genomics, and proteomics technologies, host factors participating in viral life cycles have been identified rapidly in recent years. In this review, we summarize the recent advances in virus-host cell interactions in positive-strand RNA virus infections and focus on host factors that facilitate viral replication.