The emergence and transmission of antibiotic resistance is a global public health crisis with significant burden on healthcare systems, resulting in high mortality and economic costs. In 2019, almost five million deaths were associated with drug-resistant infections, and if left unchecked, the global economy could lose $100 trillion by 2050. To effectively combat this crisis, it is essential for all countries to understand the current situation of antibiotic resistance. In this review, we examine the current driving factors leading to the crisis, impact of critical superbugs in three regions, and identify novel mechanisms of antibiotic resistance. It is crucial to monitor the phenotypic characteristics of drug-resistant pathogens and describe the mechanisms involved in preventing the emergence of cross-resistance to novel antimicrobials. Additionally, maintaining an active pipeline of new antibiotics is essential for fighting against diverse antibiotic-resistant pathogens. Developing antibacterial agents with novel mechanisms of action is a promising way to combat increasing antibiotic-resistant pathogens.