Inhalation therapy has been reported as the most effective treatment for respiratory bacterial infections due to the increasing relevance of drug bioavailability. Drug delivery systems (DDS) have the capacity to overcome pulmonary biological barriers limiting the bioavailability of inhaled anti-infectives. This is important to eradicate bacterial infections and to prevent the development of bacterial resistance. Despite substantial efforts in the field, the current state-of-the-art often fails to achieve those goals, and we still observe increasing bacterial resistance. We give a brief insight on benefits and challenges in pulmonary delivery of anti-infectives. In the context of drug delivery development for pulmonary infections, particularly focusing on Pseudomonas aeruginosa (PA) infections, this mini review will critically discuss the main requirements, as well as the recent strategies of drug delivery system synthesis and preparation. Finally, interaction of DDS with crucial pulmonary biological barriers will be of great importance for the success of future applications of the developed DDS.