It is commonly held that the various granzymes (lethal proteases produced by cytotoxic lymphocytes) utilize their different substrate preferences to bring about various forms of target cell death. Although a considerable body of evidence supports this view, it has now become clear that human granzyme H could have evolved a proteolytic specificity that both interferes directly with adenovirus replication and prevents the virus from blocking the potent pro-apoptotic activity of granzyme B.