Two endocrine disorders, congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH), when untreated, can have devastating, irreversible and fatal outcomes. Permanent cognitive impairment, growth failure and dysmorphic appearance are seen in congenital hypothyroidism (CH) and early infant death in males with salt wasting CAH (as most females are discovered by presence of atypical genital appearance, while males appeared normal). Newborn screening (NBS) for CH was developed with broader engagement of centers, and was more rapidly adopted throughout the US and other large or developed countries, while NBS for CAH was pioneered by relatively few and was not fully adopted in the US until the initiation of Universal Expanded Newborn Screening Panel in 2005. Advances in genetic understanding of CH and CAH continue with NBS. Cost–benefit analysis, showing CH NBS as more successful than CAH NBS, may not fully recognize the cost of a life saved with CAH NBS. Early treatment of CH is much simpler with taking a pill a day unlike CAH requiring multiple medication doses, and possibly surgery apart from enteral and parenteral stress doses during adrenal crisis. CAH management outcomes with gender identity matters in persons with atypical genital appearance and androgen effects are still being studied.