Retinopathy of prematurity or ROP is the leading cause of vision loss in preterm infants. Timely screening and treatment of ROP can improve the visual outcome in infants. Hence, preterm infants are repeadetly exposed to proven stressful and painful screening procedures. After a long-held belief that premature infants do not feel pain and stress was proven contrary, researches about possible repercussions of stress and pain on infant development were initiated. Numerous studies reveal that recurrent pain can have direct and long-term consequences on the neurological and behavioral development of newborns. Strategies to reduce stress and treat pain are crucial in promotion of growth and development, as well as minimizationof longterm consequences. Procedural analgesia should include the concepts of developmental care, non-nutritive sucking, pharmacological and other listed nonpharmacological agents. Unfortunately, the literature does not provide clear evidence that interventions such as anesthetic drops, oral sucrose (or glucose, or dextrose), non-nutritive sucking, and positioning are beneficial in reduction of stress (discomfort) due to ophthalmic examination for ROP. None of the interventions by itselfdemonstrated a significant change in score points on the pain assessment scale. Due to many unknown factorsabout pharmacokinetics, action and side effects of drugs used to relieve stress, it is necessary to consider the benefits versus harms to premature infants. Consequently, when screening for ROP, only a local anesthetic and / or sucrose is often used, attested to be an insufficient stress reliever. Current knowledge provides us several possible methods, pharmacological and nonpharmacological, that can be used without significant risk. It is recommended to use those methods alternately, in combinations proven to be most effective in our environment. Rapid advances in technology and the expansion of knowledge about the disease and underlying genetics, together with the growing need for effective and timely ROP assessments, may completely transform the current diagnostic approach in the near future. Our goal is primarily to use new tools to reduce the number of premature infants that need to be examined and then the number of requisite examinations in order to avoid unnecessary stress and discomfort for the infant, children who need to be examined reduce discomfort and stress.