Each year more than 350,000 babies acquire HIV infection from their mother, mainly in Africa. As sadly constant as this fact is, the policy environment around crafting an effective response has changed rapidly and unpredictably. Sequential advances in antiretroviral therapy, preserving effectiveness with far more practical regimens, have repeatedly upped the ante for action, and have also transformed policy issues. In this paper, the authors relate a modeling story--something of a saga in its meandering course--closely intertwined with evolving policy. Their models have achieved a modicum of success. They have framed several policy discussions and have at least once led directly to an important policy development. The authors have identified four essential elements of their success: (1) solid modeling, which establishes credibility; (2) connected and savvy collaborators, who permit them to reach key decisionmakers (both logistically and in the sense of gaining their serious interest); (3) their policy orientation, which has kept the models practical; and (4) quick adaptations of the model, allowing their participation in fast-moving policy developments. The models portray the risk of mother-to-child HIV transmission during pregnancy, delivery, and breast-feeding. They also portray the reduction in risk associated with the use of antiretroviral therapy (typically a 40 to 60 percent reduction), and with use of formula feeding instead of breast-feeding. Finally, the models estimate the costs of HIV testing, intervention, and HIV disease in children--in order to estimate the net costs per HIV infection averted and per Disability Adjusted Life Year (DALY) gained. The models are readily adjusted for local differences in the prevalence of HIV infection in child-bearing women, and for the likelihood of intervention initiation and completion. (Contains 2 figures and 1 footnote.)