Global developmental delay and mental retardation or intellectual disability offer challenges to the practitioner at several different levels. Accurate recognition of these most common of subtypes of neurodevelopmental disabilities is a central precondition to their correct evaluation and management. Proper evaluation is a time- and labor-intensive process that emphasizes several different goals. Guidelines now exist to assist the practitioner in selecting the appropriate investigation path to be pursued, and these guidelines should be used to inform the selections of investigations made. Although challenging and time consuming, the evaluation of these children offers many professional rewards and is a necessary first step in a family’s adaptation to their child’s chronic condition.