Pseudomonas aeruginosa is an opportunistic pathogen with a multidrug-resistant profile that has become a critical threat to global public health. It is one of the main causes of severe nosocomial infections, including ventilator-associated pneumonia, chronic infections in patients with cystic fibrosis, and bloodstream infections in immunosuppressed individuals. Development of vaccines against P. aeruginosa is a major challenge owing to the high capacity of this bacterium to form biofilms, its wide arsenal of virulence factors (including secretion systems, lipopolysaccharides, and outer membrane proteins), and its ability to evade the host immune system. This review provides a comprehensive historical overview of vaccine development efforts targeting this pathogen, ranging from early attempts in the 1970s to recent advancements, including vaccines based on novel proteins and emerging technologies such as nanoparticles and synthetic conjugates. Despite numerous promising preclinical developments, very few candidates have progressed to clinical trials, and none have achieved final approval. This panorama highlights the significant scientific efforts undertaken and the inherent complexity of successfully developing an effective vaccine against P. aeruginosa.