Microbial resistance is a serious threat to human health worldwide. Among the World Health Organisation's list of priority resistant bacteria, three are listed as critical-the highest level of concern-and all three are Gram-negative. Gram-negative resistance has spread worldwide via a variety of mechanisms, the most problematic being via AmpC enzymes, extended-spectrum beta-lactamases, and carbapenemases. A combination of older drugs, many with high levels of toxicity, and newer agents are being used to combat multidrug resistance, with varying degrees of success. This review discusses the current treatments for multidrug-resistant Gram-negative bacteria, including new agents, older compounds, and new combinations of both, and some new treatment targets that are currently under investigation.