Real-time monitoring of health conditions is an emerging strong issue in health care, internet information, and other strongly evolving areas. Wearable electronics are versatile platforms for non-invasive sensing. Among a variety of wearable device principles, fiber electronics represent cutting-edge development of flexible electronics. Enabled by electrochemical sensing, fiber electronics have found a wide range of applications, providing new opportunities for real-time monitoring of health conditions by daily wearing, and electrochemical fiber sensors as explored in the present report are a promising emerging field. In consideration of the key challenges and corresponding solutions for electrochemical sensing fibers, we offer here a timely and comprehensive review. We discuss the principles and advantages of electrochemical sensing fibers and fabrics. Our review also highlights the importance of electrochemical sensing fibers in the fabrication of “smart” fabric designs, focusing on strategies to address key issues in fiber-based electrochemical sensors, and we provide an overview of smart clothing systems and their cutting-edge applications in therapeutic care. Our report offers a comprehensive overview of current developments in electrochemical sensing fibers to researchers in the fields of wearables, flexible electronics, and electrochemical sensing, stimulating forthcoming development of next-generation “smart” fabrics-based electrochemical sensing.