The process of "structure-switching" enables biomolecular switches to function as effective biosensing tools. Biomolecular switches can be activated or inactivated by binding to a specific target that triggers a precise conformational change in the biomolecules involved. Although many examples of aptamer-based biomolecular switches can be found in nature, substantial effort has been made in the last decade to engineer structure-switching aptamer sensors by coupling aptamers to a signal transduction method to generate a readout signal upon target binding to the aptamer domain. This chapter focuses on the progress of research on engineered structure-switching aptamer sensors. We begin by discussing the origin of the structure-switching aptamer design, highlight the key developments of structure-switching DNA aptamers for fluorescence-, electrochemistry-, and colorimetry-based detection, and introduce our recent efforts in exploring RNA aptamers to create structure-switching molecular sensors.