Owing to its activity against multidrug-resistant gram-negative bacteria, colistin (like other older antibiotics) is experiencing a surprising resurgence. In the 50 years following its discovery, little effort was put into studying its dosing and pharmacodynamic properties. Recent data have been filling the gaps, and individualized dosing recommendations targeting an optimal AUC/MIC ratio have been published. According to these data, pharmacokinetic targets will clearly be missed without exceeding the currently recommended dosages. Even the highest doses studied so far do not universally result in sufficient drug levels. Therefore, colistin remains a last-resort drug which should be used in combination with other antibiotics only. Regardless of the presence of resistance, carbapenems seem to be the most promising combination partners.