All the currently available antiviral agents used in the treatment of double-stranded (ds) DNA viruses, with the exception of interferon-α, inhibit the same target, the viral DNA polymerase. With increasing reports of the development of resistance of herpes simplex virus (HSV), cytomegalovirus (CMV), and hepatitis B virus (HBV) to some of these drugs, new antiviral agents are needed to treat these infections. Additionally, no drugs have been approved to treat several DNA virus infections, including those caused by adenovirus, smallpox, molluscum contagiosum, and BK virus. We report the status of 10 new antiviral drugs for the treatment of dsDNA viruses. CMX-001 has broad activity against dsDNA viruses; 3 helicase-primase inhibitors, maribavir, and FV-100 have activity against certain herpesviruses; ST-246 inhibits poxviruses; GS-9191 inhibits papillomaviruses; and clevudine and emtricitabine are active against HBV. Most of these drugs have completed at least phase I trials in humans, and many are in additional clinical trials.