Spontaneous and sustained ("elite," or aviremic) control of HIV infection (ie, maintaining HIV RNA to less than 50 copies/mL in the absence of therapy) appears to occur in approximately 1 in 300 HIV-infected persons, and represents a distinct phenotype among HIV-infected individuals. Through a recently established international collaboration called the HIV Controller Consortium, over 300 elite controllers have been identified and blood samples collected. These ongoing studies will not only examine the immune responses to HIV that elite controllers generate, but will also make use of a newly available approach to defining the genetic basis of disease. Specifically, the consortium is attempting to determine the genetic basis underlying spontaneous control by performing whole genome analysis scans together with functional immunology studies in a large population of elite controllers. The goal of these studies is to provide insights that will help define the crucial parameters present in persons who are able to control HIV infection, similar to the control most people have with Epstein-Barr virus and varicella, namely by holding the virus in check. These findings could assist in the development of vaccines and new therapies. This article summarizes a presentation on spontaneous control of HIV infection and its implications for vaccine development made by Bruce D. Walker, MD, at an International AIDS Society-USA Continuing Medical Education course in New York in March 2007. The original presentation is available as a Webcast at www.iasusa.org.