A delay in meeting developmental milestones may be secondary to perinatal events, involving complicated interactions between mother and fetus during delivery. Maternal factors including weight, diet, and morbidities can affect neonatal adaptation and later development. Prematurity, low birth weight, and previous intrauterine insults as well as complications during delivery of a previously normal fetus increase the risk for perinatal stress. In this article, the literature on perinatal and early postnatal factors that underlie risks for developmental delay and disabilities is reviewed. Studies that concern neuroprotective therapies and prediction of long-term neurologic outcome by clinical examination, neuroimaging techniques, and electroencephalographic studies are reviewed as well. © 2013 Wiley Periodicals, Inc. Dev Disabil Res Rev 2011;17:59–70.