This longitudinal study examined genetic and caregiving contributions to individual differences in infant attachment classifications. Mothers’ responsiveness to their 6-month-old infants was rated during naturalistic interactions for 154 mother-infant pairs, and infants’ attachment organization was classified using the Strange Situation Procedure at 12 and 18 months old. Children were later genotyped with respect to the serotonin transporter linked polymorphic region (5-HTTLPR). Maternal responsiveness uniquely predicted infants’ attachment security. Infants’ 5-HTTLPR variation uniquely predicted the subtypes of attachment security or insecurity at 12 months as well as the subtype of insecurity at 18 months. The 5-HTTLPR short allele was consistently associated with attachment classifications characterized by higher emotional distress. These findings suggest that infants’ 5-HTTLPR variation contributes to infants’ emotional reactivity while the history of caregiving quality impacts how effectively infants use their caregiver for emotional regulation. Theoretical implications for the study of genetic and caregiving influences are discussed.