Classic CAH (salt-wasting and simple virilizing) meets all of the recommended criteria for newborn screening. There are reliable and efficient newborn screening tests, the disorder results in high morbidity and mortality if left undetected, there is effective treatment that reduces negative outcomes, and there is a relatively high incidence. When compared with the case findings without the benefit of screening, the data from screening programs show reduced adrenal crises, reduced incorrect sex assignments, and reduced deaths. Racial/ethnic prevalence differences are present in newborn screening program data. The Texas data indicate a lower disease frequency in African-Americans when compared with Caucasians, and international data indicate higher frequencies in native Yupik Eskimos, Brazilians, residents of La Reunion, and Filipinos. When worldwide clinical ascertainment data are compared with newborn screenng data, it is clear that newborns with CAH (especially males) die when screening is not done. To be effective in reducing mortality, newborn screening must be performed soon after birth, and the results must be available quickly so that early salt-wasting crises can be averted. It is preferable that newborn screening laboratiories be operational 7 days a week, and that sample delivery from the collection site to testing laboratory be as efficient as possible, including weekends and holidays, so that undue testing delays are not encountered. These two requirements pose major challenges for most programs, but they are critical to optimal screening outcome. Based on the studies in Texas, with second screening samples collected at approximately 2 weeks of age, some newborns with simple virilizing CAH are missed on initial screening using current testing protocols. There is need to set a screening cut-off such that the false-positive rate does not oversaturate the follow-up system, in part owing to the insensitivity of current kit methodologies and the biochemical manifestations of CAH. With advances in genetic testing procedures and improved automation techniques, it may soon be possible for CAH screening programs to include genotyping as a second-tier confirmation as a part of the newborn screening protocol. Despite the fact that CAH is a continuum of disorders, the correlation between genotype and phenotype is fairly consistent in most cases. For the purpose of screening, genotyping will likely be useful only for differential diagnoses of non-salt wasters, given the necessary time constraints and expense of obtaining genotypes and the need for immediate diagnosis/treatment of salt wasters. It is hoped that newborn screening programs will begin to provide answers to some of these question in addition to their primary function of reducing the morbidity and mortality resulting from CAH.