This review paper discusses electrochemical biosensors, focusing on their principles, architectures, and applications. Electrochemical biosensors are attractive for analyzing biological samples due to their ability to directly convert biological events into electronic signals. Over the past decades, various sensing techniques have been developed, including cyclic voltammetry, chronoamperometry, chronopotentiometry, impedance spectroscopy, and field-effect transistor-based methods. Novel approaches such as nanowire and magnetic nanoparticle-based biosensing are also highlighted. Additional techniques like surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz crystal microbalance, and scanning probe microscopy are summarized as complementary methods useful in combination with electrochemical detection. The performance of electrochemical sensors is often determined by surface architectures that connect the sensing element to the biological sample at the nanometer scale. Surface modification techniques, electrochemical transduction mechanisms, and the choice of recognition receptor molecules all influence the sensor's sensitivity. New nanotechnology-based approaches, such as engineered ion channels in lipid bilayers, enzyme encapsulation in vesicles, polymersomes, or polyelectrolyte capsules, provide additional possibilities for signal amplification. The review emphasizes the importance of precise control over the interplay between surface nano-architectures, surface functionalization, and the chosen sensor transducer principle. Complementary characterization tools are also useful for interpreting and optimizing sensor responses. Electrochemical biosensors have advantages such as robustness, easy miniaturization, excellent detection limits, and the ability to be used in turbid biofluids. However, challenges remain in achieving high sensitivity and unique identification of the response with the desired biochemical event. The review discusses various electrochemical detection techniques, including amperometry, potentiometry, and conductometry. Amperometric devices measure current resulting from the oxidation or reduction of an electroactive species, while potentiometric devices measure the accumulation of a charge potential. Conductometric devices measure the ability of an analyte or medium to conduct an electrical current. These techniques are reviewed in the context of biosensing applications, with examples of their use in detecting various analytes. The review also covers field-effect transistors (FETs) and their use in biosensing, as well as the application of nanowires in biosensors. Nanowires are reviewed for their versatile roles in electrochemical biosensing and bioelectronic applications. Their small size and high surface-to-volume ratio make them attractive for biosensing due to their sensitivity to surface perturbations. The review highlights the potential of nanowires in biosensing, including their use in detecting DNA hybridization, pH, protein, and DNA binding. The integration of nanowires in FET devices and arrays is also discussed as a means to achieve multi-analyte biosensing.This review paper discusses electrochemical biosensors, focusing on their principles, architectures, and applications. Electrochemical biosensors are attractive for analyzing biological samples due to their ability to directly convert biological events into electronic signals. Over the past decades, various sensing techniques have been developed, including cyclic voltammetry, chronoamperometry, chronopotentiometry, impedance spectroscopy, and field-effect transistor-based methods. Novel approaches such as nanowire and magnetic nanoparticle-based biosensing are also highlighted. Additional techniques like surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz crystal microbalance, and scanning probe microscopy are summarized as complementary methods useful in combination with electrochemical detection. The performance of electrochemical sensors is often determined by surface architectures that connect the sensing element to the biological sample at the nanometer scale. Surface modification techniques, electrochemical transduction mechanisms, and the choice of recognition receptor molecules all influence the sensor's sensitivity. New nanotechnology-based approaches, such as engineered ion channels in lipid bilayers, enzyme encapsulation in vesicles, polymersomes, or polyelectrolyte capsules, provide additional possibilities for signal amplification. The review emphasizes the importance of precise control over the interplay between surface nano-architectures, surface functionalization, and the chosen sensor transducer principle. Complementary characterization tools are also useful for interpreting and optimizing sensor responses. Electrochemical biosensors have advantages such as robustness, easy miniaturization, excellent detection limits, and the ability to be used in turbid biofluids. However, challenges remain in achieving high sensitivity and unique identification of the response with the desired biochemical event. The review discusses various electrochemical detection techniques, including amperometry, potentiometry, and conductometry. Amperometric devices measure current resulting from the oxidation or reduction of an electroactive species, while potentiometric devices measure the accumulation of a charge potential. Conductometric devices measure the ability of an analyte or medium to conduct an electrical current. These techniques are reviewed in the context of biosensing applications, with examples of their use in detecting various analytes. The review also covers field-effect transistors (FETs) and their use in biosensing, as well as the application of nanowires in biosensors. Nanowires are reviewed for their versatile roles in electrochemical biosensing and bioelectronic applications. Their small size and high surface-to-volume ratio make them attractive for biosensing due to their sensitivity to surface perturbations. The review highlights the potential of nanowires in biosensing, including their use in detecting DNA hybridization, pH, protein, and DNA binding. The integration of nanowires in FET devices and arrays is also discussed as a means to achieve multi-analyte biosensing.