Electrochemical biosensing, due to its sensitivity and specificity, combined with the low-cost and operation convenience of the equipment, is considered as a promising point-of-care approach in clinical analysis. This review presents the basic principles of operation, the current status, and the trends in the development and the clinical implementation of some selected electrochemical biosensors. These include: electrochemical glucose biosensors successfully applied in diabetes management, and electrochemical biosensors for cholinesterases and trypsin activities determination. The latter, although less common, demonstrate the potential of improving the existing clinical methods in the diagnostics and the treatment of neurotoxic, neurological, and pancreatic diseases.