The rapid implementation and continuing expansion of forensic DNA databases around the world has been supported by claims about their effectiveness in criminal investigations and challenged by assertions of the resulting intrusiveness into individual privacy. These two competing perspectives provide the basis for ongoing considerations about the categories of persons who should be subject to non-consensual DNA sampling and profile retention as well as the uses to which such profiles should be put. This paper uses the example of the current arrangements for forensic DNA databasing in England and Wales to discuss the ways in which the legislative and operational basis for police DNA databasing is reliant upon continuous deliberations over these and other matters by a range of key stakeholders. We also assess the effects of the recent innovative use of DNA databasing for “familial searching” in this jurisdiction in order to show how agreed understandings about the appropriate uses of DNA can become unsettled and reformulated even where their investigative effectiveness is uncontested. We conclude by making some observations about the future of what is recognized to be the largest forensic DNA database in the world.