An essential part of current medical diagnosis is reliable multiplexed determination of clinical relevant biomarkers at different molecular level that allows the evaluation of the pathological stage and differential patient diagnosis. Within this context, electrochemical immunosensors have proven to offer significant advantages compared to conventional methodologies for this purpose, in terms of cost, portability, easy use, rapid readout, and amenability to direct and multiplexing analysis in complex samples. In addition, these devices are easy to manufacture, implemented using cost-effective instrumentation and automation, which makes them suitable for implementing as point-of-care (POC) systems and/or utilization in undeveloped areas. Considering this rapid moving and highly interesting field, this chapter offers an updated overview describing with critical arguments the special features and opportunities currently provided by electrochemical immunosensing for multiplexed determination in clinical diagnosis by highlighting recent advances and key points to satisfy the current POC immunodiagnosis demands. Main objectives pursued in the field, which included the development of multiplexed and integrated systems to allow a more reliable identification/diagnosis and meet the POC testing (POCT) and routine analysis requirements will be didactically described. The variety of amplification strategies involving nanomaterials and attractive surface modification protocols will be described with special attention, as well as those challenging applications, some of them in a pioneering way in the field of electrochemical immunosensors, are successfully addressed. Furthermore, current progress and chances supplied for multiplexing detection at different molecular levels and the challenges that must be faced to bring them to market and future prospects will also be commented.