Multi-drug resistant (MDR) strains of Salmonella enterica serovar Typhimurium are of increasing concern in the food industry and on the farm. While these strains are becoming increasingly resistant to commonly used antimicrobial agents, they remain sensitive to killing by their natural predators, bacteriophage. Bacteriophage are able kill MDR strains of Salmonella in vitro. We have recently tested the ability of a well-known salmonella bacteriophage, Felix 01 and two recently isolated phage (HL03 and HL18) to reduce the Salmonella Typhimurium burden in orally challenged, susceptible mice. When each of the phage was given at the same time as the oral Salmonella challenge, they significantly reduced the Salmonella burden in the treated mice. This lowering of Salmonella load occurred when the phage were given at a 1:10, 1:50 and 1:100 MOI when compared to the bacterial challenge dose. Interestingly, of the three phage tested (Felix, HL03 and HL18), only the last phage, HL18 was effective when given an hour before or an hour after Salmonella challenge. Felix01 and HL03 were both ineffective when given an hour before or an hour after challenge, but consistently lowered the bacterial burden in these mice when given at the same time as the challenge dose. These data indicate that bacteriophage-based therapy may be an alternative to antibiotic-based treatments to lower the Salmonella levels in swine and potentially limit the spread of Salmonella during transport and lairage of swine prior to slaughter.