This review delves into the titanic research efforts carried out during the last years on affinity-based wearable electrochemical biosensors, using both natural (antibodies) and biomimetic (aptamers, peptides and molecular imprinted polymers) receptors. The rationale and application of selected representative strategies is critically discussed, ending with realistic and futuristic visions of the technical barriers, challenges and prospects in the development and adoption of these biodevices in daily routines to ensure well-being against known, unknown and unexpected threats.