Antimicrobial resistance of bacteria causing pediatric infections has become more common and complicated in recent years. Although formerly confined to hospital settings, multi-drug resistant bacteria now also cause community-acquired infections. Treatment of infections caused by resistant pathogens is difficult, necessitating thinking both inside and outside the box. Determination of the precise minimal inhibitory concentration (MIC) is often crucial for selecting the most appropriate antibiotics, their doses, and use of prolonged infusions. For some multiply-resistant bacteria, off-label use of antibiotics, sometimes with no evidence from controlled studies ("salvage therapy") is unavoidable.