The replication efficacy of several DNA and RNA viruses, including human respiratory syncytial virus (RSV), depends on the activation of the Raf/MEK/ERK signaling cascade. Here, we demonstrate that the late-stage activation of ERK is associated with surface accumulation of the RSV fusion protein F. Interestingly, MEK inhibition resulted in impaired accumulation of the F protein at the cellular surface and was associated with reduced viral titers, indicating the Raf/MEK/ERK kinase cascade as potential target for antiviral intervention.