The emergence of multidrug-resistant strains of gram-negative bacilli during the last decade has generated renewed interest in older antimicrobials that had been relegated to a second line because of a poorer safety profile, but that are still active against these microorganisms. Once-daily administration of aminoglycosides has limited the toxicity of these agents and enabled their reintroduction into clinical practice. Recent studies have shown no additional benefits of concomitant administration of aminoglycosides with current ss-lactams, and the available evidence does not support the use of once-daily administration for all indications. The new formulations and dosages of polymyxins have also reduced the toxicity rates attributed to these agents in the past. Although more extensive studies are required to properly define their pharmacokinetics and effectiveness, the available data have shown favorable outcomes for patients with infection due to multiresistant gram-negative bacilli treated with colistin, either alone or combined with other antimicrobial agents.