Until recently, the polymyxin antibiotics were used sparingly due to dose limiting toxicities. However, the lack of therapeutic alternatives for infections caused by highly resistant Gram-negative bacteria has led to the increased use of the polymyxins. Unfortunately, the world has witnessed increased rates of polymyxin resistance in the last decade, which is likely in part due to its irrational use in human and veterinary medicine. The spread of polymyxin resistance has been aided by the dissemination of the transferable polymyxin-resistance gene, mcr, in humans and the environment. The mortality of colistin-resistant bacteria (CoRB) infections varies in different reports. However, poor clinical outcome was associated with prior colistin treatment, illness severity, complications, and multidrug resistance. Detection of polymyxin resistance in the clinic is possible through multiple robust and practical tests, including broth microdilution susceptibility testing, chromogenic agar testing, and molecular biology assays. There are multiple risk factors that increase a person's risk for infection with a polymyxin-resistant bacteria, including age, prior colistin treatment, hospitalization, and ventilator support. For patients that are determined to be infected by polymyxin-resistant bacteria, various antibiotic treatment options currently exist. The rising trend of polymyxin resistance threatens patient care and warrants effective control.