pH-sensing materials and configurations are rapidly evolving toward exciting new applications, especially those in biomedical applications. In this review, we highlight rapid progress in electrochemical pH sensors over the past decade (2008–2018) with an emphasis on key considerations, such as materials selection, system configurations, and testing protocols. In addition to recent progress in optical pH sensors, our main focus in this review is on electromechanical pH sensors due to their significant advances, especially in biomedical applications. We summarize developments of electrochemical pH sensors that by virtue of their optimized material chemistries (from metal oxides to polymers) and geometrical features (from thin films to quantum dots) enable their adoption in biomedical applications. We further present an overview of necessary sensing standards and protocols. Standards ensure the establishment of consistent protocols, facilitating collective understanding of results and building on the current state. Furthermore, they enable objective benchmarking of various pH-sensing reports, materials, and systems, which is critical for the overall progression and development of the field. Additionally, we list critical issues in recent literary reporting and suggest various methods for objective benchmarking. pH regulation in the human body and state-of-the-art pH sensors (from ex vivo to in vivo) are compared for suitability in biomedical applications. We conclude our review by (i) identifying challenges that need to be overcome in electrochemical pH sensing and (ii) providing an outlook on future research along with insights, in which the integration of various pH sensors with advanced electronics can provide a new platform for the development of novel technologies for disease diagnostics and prevention.