Powdered infant formula is not sterile and may be intrinsically contaminated with pathogens, such as Salmonella enterica, that can cause serious illness in infants. In recent years, at least 6 outbreaks of Salmonella infection in infants that have been linked to the consumption of powdered infant formula have been reported. Many of these outbreaks were identified because the Salmonella strains were unique in some way (e.g., a rare serotype) and a well-established Salmonella surveillance network, supported by laboratories capable of serotyping isolates, was in place. Another common feature of the outbreaks was the low level of salmonellae detected in the implicated formula (salmonellae may be missed in routine testing). These outbreaks likely represent only a small proportion of the actual number of Salmonella infections in infants that have been linked to powdered infant formula. Managing this problem requires a multidimensional approach in which manufacturers, regulators, and caregivers to infants can all play a role.