Chronic infections often contain complex polymicrobial communities that are recalcitrant to antibiotic treatment. The pathogens associated with these infectious communities are often studied in pure culture for their ability to cause disease. However, recent studies have begun to focus on the role of polymicrobial interactions in disease outcomes. Pseudomonas aeruginosa can colonize patients with chronic lung diseases for years and sometimes even decades. During these prolonged infections, P. aeruginosa encounters a plethora of other microbes including bacteria, fungi, and viruses. The interactions between these microbes can vary greatly, ranging from antagonistic to synergistic depending on specific host and microbe-associated contexts. These additional layers of complexity associated with chronic P. aeruginosa infections must be considered in future studies in order to fully understand the physiology of infection. Such studies focusing on the entire infectious community rather than individual species may ultimately lead to more effective therapeutic design for persistent polymicrobial infections.