Cystic fibrosis is the most common autosomal recessive disease among Caucasians. It is caused by mutations in the CFTR gene whose product is a chloride channel protein, found on epithelial cells' membrane of many organs. The mutation leads to formation of thick, viscous mucus which causes organ dysfunction. Diagnosis of cystic fibrosis relies on recognition of clinical symptoms but at that point some organ damage can already be permanent. Newborn screening is a method offering an opportunity for diagnosis of asymptomatic infants enabling early treatment and prevention or delay of disease symptoms, such as malnutrition, poor growth, vitamin deficiency and reduced lung function. Early treatment provides better lung function, which is the main lifespan predictor. Screening protocol consists of different combinations of dried blood spot lRT measurement and DNA-testing, followed always by the sweat test to confirm the diagnosis in newborn screened-positive. Great number of known mutations and their ethnic and geographic diversity as well as possible borderline sweat test results lead to inconclusive screening results in some cases. This challenges protocol development and raises question regarding cost-effectiveness of including cystic fibrosis screening in national programmes. However, long-term studies speak in favour of screening implementation, mainly because of the favourable impact early diagnosis has on patient's general health and life-span. Screening protocol should be adjusted to demographic characteristics of the tested population and technical resources. Finally yet importantly, the health system must insure continous multidisciplinary treatment and follow-up for patients diagnosed through screening, as well as for screened positive individuals with inconclusive diagnosis.