Entry into host cells is a strategy widely used by bacterial pathogens, after which they either remain within membrane-bound compartments or rupture the endocytic vacuole to reach the cytoplasm. During recent years, cytoplasmic access has been documented for an increasing number of pathogens. Here we review how classical cytoplasmic bacterial pathogens rupture their endocytic vacuoles as well as the mechanisms used to accomplish this task by bacterial species for which host cytoplasmic localization has only recently been identified. We also discuss the consequences for pathogenesis resulting from this change in intracellular localization, with a particular focus on the role of the host. What emerges is that cytoplasmic access plays an important role in the pathophysiology of an increasing number of intracellular bacterial pathogens.