Pseudomonas aeruginosa remains a major cause of bloodstream infections associated with high mortality. Adequacy of empirical therapy seems to influence outcome. Because of its high intrinsic resistance and its capacity to develop resistance during therapy, exposure to antimicrobial therapies frequently leads to subsequent P. aeruginosa bacteraemia with resistant isolates, increasing the risk of inadequate empirical therapy. Therefore empirical therapy should not include antimicrobial agents used in the last few months. Definitive combination therapy does not influence the prognosis of P. aeruginosa bacteraemia. Similarly, empirical combination therapy does not improve survival until receipt of the antibiogram. In contrast, empirical combination therapy does improve survival from the day of receipt of antibiogram to day 30. We therefore suggest that patients suspected of P. aeruginosa bacteraemia should receive empirical combination therapy until receipt of the antibiogram, followed by downgrading to an adequate monotherapy. This strategy might reduce mortality in P. aeruginosa bloodstream infections without exposing the patient to an excessive risk of adverse events. Antimicrobial therapies might select P. aeruginosa isolates with particular virulence phenotypes. The influence of specific virulence determinants on the prognosis of P. aeruginosa bacteraemia, as well as the potential benefit of virulence inhibition, deserves further investigation.