OBJECTIVE: In 1995, the United States was the first country to introduce a universal 1-dose childhood varicella vaccination program. In 2006, the US varicella vaccine policy was changed to a routine 2-dose childhood program, with catchup vaccination for older children. The objective of this review was to summarize the US experience with the 1-dose varicella vaccination program, present the evidence considered for the policy change, and outline future challenges of the program. METHODS: We conducted a review of publications identified by searching PubMed for the terms "varicella," "varicella vaccine," and "herpes zoster." The search was limited to US publications except for herpes zoster; we reviewed all published literature on herpes zoster incidence. RESULTS: A single dose of varicella vaccine was 80% to 85% effective in preventing disease of any severity and >95% effective in preventing severe varicella and had an excellent safety profile. The vaccination program reduced disease incidence by 57% to 90%, hospitalizations by 75% to 88%, deaths by >74%, and direct inpatient and outpatient medical expenditures by 74%. The decline of cases plateaued between 2003 and 2006, and outbreaks continued to occur, even among highly vaccinated school populations. Compared with children who received 1 dose, in 1 clinical trial, 2-dose vaccine recipients developed in a larger proportion antibody titers that were more likely to protect against breakthrough disease and had a 3.3-fold lower risk for breakthrough disease and higher vaccine efficacy. Two studies showed no increase in overall herpes zoster incidence, whereas 2 others showed an increase. CONCLUSIONS: A decade of varicella prevention in the United States has resulted in a dramatic decline in disease; however, even with high vaccination coverage, the effectiveness of 1 dose of vaccine did not generate sufficient population immunity to prevent community transmission. A 2-dose varicella vaccine schedule, therefore, was recommended for children in 2006. Data are inconclusive regarding an effect of the varicella vaccination program on herpes zoster epidemiology.