Intracellular pathogenic bacteria can lead to some of the most life-threatening infections. By evolving a number of ingenious mechanisms, these bacteria have the ability to invade, colonize and survive in the host cells in active or latent forms over prolonged period of time. A variety of nanoparticulate systems have been developed to optimize the delivery of antibiotics. Main advantages of nanoparticulate systems as compared with free drugs are an efficient drug encapsulation, protection from inactivation, targeting infection sites and the possibility to deliver drugs by overcoming cellular barriers. Nevertheless, despite the great progresses in treating intracellular infections using nanoparticulate carriers, some challenges still remain, such as targeting cellular subcompartments with bacteria and delivering synergistic drug combinations. Engineered nanoparticles should allow controlling drug release both inside cells and within the extracellular space before reaching the target cells.