Antimicrobial resistance is a global medical problem, affecting most bacterial pathogens. The major challenges are currently posed by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterobacteriaceae producing extended-spectrum-beta-lactamases (ESBL) and carbapenemases, and multi-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Therapeutic options are very limited and, in some cases, virtually unavailable. This article provides an overview of the recent epidemiological trends exhibited by the most important multi-resistant pathogens, and of the treatment options that are currently available for these infections.