Objective: To provide a comprehensive evaluation of accelerated immunotherapy build-up schedules in terms of adverse reactions and clinical efficacy. Data Sources: Peer-reviewed studies and review articles were selected from the PubMed database for articles published in the years 1976 to 2006 using the following keywords: rush, cluster immunotherapy in combination with allergic rhinitis, asthma, Hymenoptera, and imported fire ant. Study Selection: Studies were selected if they provided safety and efficacy information on accelerated allergen immunotherapy schedules. Most of the studies reviewed were double-blind, placebo controlled, but some open-observational studies were included if they provided immunotherapy safety or other information the author thought was relevant. Results: A wide range of systemic reactions were reported in the literature with inhalant allergens: ranging from 27% to 100% of the patients in rush immunotherapy studies and 0% to 79% of patients in the cluster studies. Predictors of systemic reactions with rush immunotherapy were forced expiratory volume in 1 second less than 80% of predicted and a high degree of skin test reactivity. Premedication clearly reduces the risk of systemic reactions with rush immunotherapy, but the effect on cluster schedules was not as clear. Conclusion: Accelerated immunotherapy build-up schedules in selected patients may provide a rapid alternative to conventional build-up schedules without a significant increase in risk.