Transcriptional activation of many developmentally regulated genes is mediated by proteins binding to enhancer sequences located several kilobases from the promoter. Existing models for how activator proteins function do not adequately explain long-range activation. Recent experiments in Drosophila on insulators that block enhancer-promoter interactions, interchromosomal activation, and mutants deficient in long-range activation are consistent with models in which facilitator factors that function between enhancers and promoters bring them into physical proximity of each other.