Substance use and alcohol abuse during pregnancy are significant public health concerns. Neonatal abstinence syndrome (NAS) is a withdrawal syndrome that infants exposed to opioids may experience in the first few days of life. For most infants with NAS, exposure to opioids occurs during pregnancy while they are fetuses. Similarly, prenatal alcohol exposure (PAE) is the most common preventable cause of intellectual and developmental delay and disabilities in the United States. Fetal alcohol spectrum disorders (FASDs) is a term used to describe preventable birth defects and intellectual/developmental disabilities resulting from PAE. This article offers a general overview of NAS assessment, management, and treatment considerations, as well as a brief overview of FASD.