Renal clearance is an important route of drug elimination. While during the neonatal period there is minimal glomerular filtration and active tubular secretion of drugs, there is a well-described rapid development in these processes in the post-neonatal period. A less appreciated fact is that during toddlerhood, there is an "overshoot" of the glomerular filtration rate (GFR) well above the levels encountered in older children and adults, and there is an early achievement of adult levels in active drug secretion, which stays at a plateau throughout childhood and adulthood with an "overshoot" in toddlers due to specific transport mechanisms. This phenomenon leads to dose requirements for renally excreted drugs in this age group being, on a per-kilogram basis, much larger than in adults. This review discusses the mechanisms related to renal ontogeny in drug handling.