Although much work remains to expand the evidence base for HIV prevention, this PWG review argues for the urgency of scaling up programs to change behavior to prevent HIV infection. The evidence on behavior change HIV prevention cannot be overstated, but it also must not be overlooked. The central problem in HIV prevention is not lack of evidence but failure to bring to scale programming that addresses the major drivers of HIV infection in specific national settings. In the 21st century, pessimism about the real challenges ahead, or concern that we do not yet have all the answers, should not stop us from preventing the next HIV infection.