P. aeruginosa is a serious cause of infection with reported rates of mortality being up to 61%. Several studies evidenced a correlation between hospital mortality due to P. aeruginosa bloodstream infections and an inappropriate antimicrobial treatment. Increasing resistance in P. aeruginosa isolates complicates the selection of adequate empirical therapy in severe infections and P. aeruginosa is often indistinguishable from other gram-negative bacterial infections. For these reasons, present guidelines for the treatment of suspected P. aeruginosa bacteraemia recommend the rapid introduction of empirical antimicrobial therapy that includes at least one antipseudomonal agent until having microbiological results. Current consensus favours the use of empirical combination, balancing the potential for greater toxicity against the lower emergence of antimicrobial resistance and the greater killing that might be achieved by combination therapies acting synergistically. Advantages and disadvantages of combination therapy towards monotherapy for P. aeruginosa severe infections, current antibiotics used for P. aeruginosa severe infections and main studies published on this issue are reviewed.