The emergence and widespread dissemination of multidrug-resistant organisms is considered one of the three most important public health threats for humankind in the 21st century and jeopardizes the practice of modern medicine. Failure to tackle this problem in a comprehensive fashion could result in a dire post-antibiotic era, impairing the future development of treatments against important diseases, such as cancer, and transplant medicine, among others. Here, we provide a global perspective of the problem and describe some of the most important antibiotic-resistant organisms affecting the health of our patients. In addition, we discuss some of the ongoing efforts to deal with the antimicrobial resistance crisis.