Salmonella enterica is a bacterial pathogen that closely interacts with its host and replicates intracellularly. It has evolved the ability to create an intracellular membrane vacuole where it can survive and replicate. The nature of the Salmonella vacuole is still poorly understood, and although it has some features in common with lysosomes, it serves as a suitable niche for its survival. In contrast to broad-host Salmonella enterica serovars, Salmonella enterica serovar Typhi (S. Typhi) is a host-adapted pathogen that does not have the ability to replicate in any species other than humans. Such host adaptation is manifested at the single cell level since this pathogen is unable to survive in non-human macrophages. We recently reported that a pathway dependent on the Rab GTPase Rab32 and its guanine-nucleotide exchange factor BLOC-3 restricts the growth and survival of S. Typhi in non-permissive macrophages. We also found that broad host Salmonellae, such as S. Typhimurium, are able to antagonize this pathway by delivering a bacterial effector protein that specifically cleaves Rab32 resulting in its degradation.