In Minnesota and other states, all newborns are screened for cystic fibrosis (CF). CF is a common genetic condition that affects the sinopulmonary, hepatobiliary and male urogenital systems. Cystic fibrosis is caused by mutations in both copies of the CF transmembrane conductance regulator (CFTR) gene. In Minnesota, infants who have elevated immunoreactive trypsinogen (IRT) at birth are tested for a panel of 39 mutations. Newborn screening detects most infants with two CFTR mutations as well as some who are CF carriers. This method of newborn screening leads to the identification of some individuals with milder forms of CFTR dysfunction whose clinical diagnosis is unclear. The Cystic Fibrosis Foundation has designated diagnostic and management guidelines for CFTR-related metabolic syndrome (CRMS) for infants who have evidence of CFTR dysfunction but who do not meet the diagnostic criteria for CF. This article discusses the clinical impact of CRMS in Minnesota.