Newborn screening is a public health program aimed at early identification of conditions for which timely intervention is expected to result in elimination or reduction of morbidity, mortality, and disabilities. Originally instituted in the 1960s for the early detection of phenylketonuria (PKU), the number of diseases screened for in the newborn period has dramatically increased with the introduction of MS/MS multiplex analyses of acylcarnitine and amino acid profiles. Newborn screening is a system and it involves a team with multidisciplinary approach. The disorders to be included in newborn screening program depend on epidemiologic burden of the disorders in the country. The advances in treatment of inborn errors of metabolism are also continuously expanding the domain of newborn screening. Although primarily targeted at detection of disorders of metabolism the screening program now also includes detection of hearing impairment and critical congenital heart disease. There are certain pitfalls in newborn screening program, but newborn screening program is the need of the hour beyond any doubt.