Our understanding of both membrane traffic in mammalian cells and the cell biology of infection with intracellular pathogens has increased dramatically in recent years. In this review, we discuss the cell biology of the host-microbe interaction for four intracellular pathogens: Chlamydia spp., Legionella pneumophila, Mycobacterium spp., and the protozoan parasite Toxoplasma gondii. All of these organisms reside in vacuoles inside cells that have restricted fusion with host organelles of the endocytic cascade. Despite this restricted fusion, the vacuoles surrounding each pathogen display novel interactions with other host cell organelles. In addition to the effect of infection on host membrane traffic, we focus on these novel interactions and relate them where possible to nutrient acquisition by the intracellular organisms.