Flexible biosensors form part of a rapidly growing research field that take advantage of a multidisciplinary approach involving materials, fabrication and design strategies to be able to function at biological interfaces that may be soft, intrinsically curvy, irregular, or elastic. Numerous exciting advancements are being proposed and developed each year towards applications in healthcare, fundamental biomedical research, food safety and environmental monitoring. In order to place these developments in perspective, this review is intended to present an overview on field of flexible biosensor development. We endeavor to show how this subset of the broader field of flexible and wearable devices presents unique characteristics inherent in their design. Initially, a discussion on the structure of flexible biosensors is presented to address the critical issues specific to their design. We then summarize the different materials as substrates that can resist mechanical deformation while retaining their function of the bioreceptors and active elements. Several examples of flexible biosensors are presented based on the different environments in which they may be deployed or on the basis of targeted biological analytes. Challenges and future perspectives pertinent to the current and future stages of development are presented. Through these summaries and discussion, this review is expected to provide insights towards a systematic and fundamental understanding for the fabrication and utilization of flexible biosensors, as well as inspire and improve designs for smart and effective devices in the future.