Electrochemical sensors have emerged as important diagnostic tools in recent years, due to their simplicity and ease of use. Compared to instrumental analysis methods that use complicated experimental and data analysis techniques─such as mass spectrometry, nuclear magnetic resonance (NMR), spectrophotometric methods, and chromatography─electrochemical sensors show promise for use in a wide range of real-time and in situ applications such as pharmaceutical testing, environmental monitoring, and medical diagnostics. In order to identify analytes in complex and/or biological samples, materials used for both the electrode materials and the chemically selective layer have been evolving throughout the years for optimizing the analytical performance of electrochemical sensors to increase sensitivity, selectivity and linear range. In this Perspective, attention will be focused on different types of materials that have been used for electrochemical sensing, including new combinations of well-studied materials as well as novel strategies to enhance the performance of sensing devices. The Perspective will also discuss existing challenges in the field and future strategies for addressing those challenges.