The increasing impact of infectious, cardiovascular and neurodegenerative diseases has intensified the demand for early and decentralized diagnostics. Label-free electrochemical biosensors are promising candidates, offering high sensitivity, low reagent consumption and miniaturizable, low-cost architectures for point-of-care (PoC) testing. This review summarizes advances in immobilization strategies, recognition elements such as DNA, antibodies, aptamers, and molecularly imprinted polymers, as well as electrode platforms including glassy carbon, screen-printed, and 3D-printed systems, with an emphasis on DNA biosensors, multiplexed configurations, and applications to disease biomarkers. Beyond analytical performance, we critically examine the barriers that keep most devices at the proof-of-concept stage, including bioreceptor stability and immobilization, limited validation in real samples, reliance on conventional materials, challenges in scalable manufacturing, transport, and storage, and the absence of fully integrated PoC systems. Finally, we discuss significant advances in sensitivity, reproducibility, and application to real samples, but note that translation to real-world use and commercialization remains limited.