Many babies are very sick at the time of birth, and in many cases the cause is unknown despite running all the tests. These newborn babies remain very sick and in the neonatal ICU without a diagnosis. Genome sequencing has come to the rescue in the face of this uncertainty. A genome sequencing test has been developed that can screen for disease-causing mutations in newborns within about 48 hours. Normally, genome sequencing can take weeks. This test can be a lifesaver for some of the newborn babies who are very sick at birth for unknown reasons. Some of these babies end up in neonatal ICU, where they struggle with life and death. Since all possible diagnostic tests fail to determine the cause of their illness, there is a very small window of opportunity to use next generation sequencing to diagnose their illness. By rapidly sequencing the entire genome or parts of the genome, a determination can be made whether there is a known or novel genetic defect, hiding among the three billion nucleotides, responsible for the newborn baby’s disease. The hope would be to find something for which there is a cure so treatment can begin immediately but that may not always happen. Nonetheless, there is some comfort in knowing what is causing the symptoms, and doctors can try to come up with some treatment plan, rather than being in the dark.