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In the 21st century, there have been radical changes in healthcare related to the transition from a universal approach to personalized medicine based on the unique characteristics of each patient. In large part, this has become possible due to the development and distribution of wearable medical devices that are capable of providing continuous monitoring of a variety of physiological parameters outside medical institutions. The most important of these devices are modern biosensors that allow real-time tracking of various biomarkers in the body, thereby opening up new opportunities for disease prevention, early diagnosis, and personalized treatment strategies. The most obvious example of the transformation is the implementation of wearable devices for continuous glucose monitoring (CGM), which has significantly facilitated the daily lives of millions of people with diabetes. Nevertheless, despite the examples of successful implementation of these devices, their large-scale distribution is associated with many challenges, such as the need for standardization, data transmission security, and the risks of immune responses to implantable devices or infections. This review examines all the current problems of wearable biosensors and possible ways to overcome them. Special emphasis will be placed on devices for continuous glucose monitoring as the most commercially successful representatives of this device class.