Bovine viral diarrhea virus (BVDV) is an important animal pathogen that establishes a lifelong persistent infection and has been regarded as a surrogate model for hepatitis C virus. It is widely accepted that BVDV has developed multiple strategies to overcome interferon responses to ensure its efficient replication in host cells. Recent studies employing yeast two-hybrid screens, pull-down and co-immunoprecipitation experiments identified viral interactions with key cell signaling pathways, such as NF-kappaB, lipid metabolism and kinases. The relevance of many of these interactions to the viral pathogenesis and persistence remains to be demonstrated. This review describes the recent findings on BVDV-host interactions.