ABSTRACT: Physical constraints and metabolic differences in neonates require that special attention is given to performing procedures in this patient group. Neonates have a thinner dermis and a greater surface-to-weight ratio, allowing for easier invasion through the skin barrier. The enzymes for metabolism of agents and defense against organisms inside the body are not fully developed in infants. Very premature neonates also have less circulating albumin, making the effective concentration of circulating agent even greater. The infant is prone to unanticipated movement during procedures, such as rolling on the procedure table. The neonatal period is the most common time period for malformations to become manifest on the skin, and invasion of some of these lesions can produce morbidity. These and other factors affect the choice of the type of procedure used, the timing for intervention, and the approach to intervention in this age group. This article reviews the important considerations for approaching procedures and offers suggestions for safe and effective methods of reliably producing the intended outcome.