The present invention is based on the discovery that interspecies quorum sensing is related to biofilm formation. The present invention provides methods useful for treating or preventing biofilm formation and microbial infections associated with biofilm formation by using an agent that either increases LuxS-dependent pathway or interspecies quorum sensing signal. The present invention also provides compositions containing an anti-microbial agent and an agent that either increases LuxS-dependent pathway or interspecies quorum sensing signal.