Chemistry has long been playing its specific role in ultrasound-responsive theranostic biomedicine in the form of microbubbles, which clinically provide the dynamic detection of macro and microvasculature by continuous expanding and contracting under the alternating ultrasound pressure. However, microbubbles' large particle size severely hinders their efficiency in ultrasound-triggered diseases theranostics as they only transport within the blood vessels. Fortunately, the scientific community recently seeks solving strategies from the advances of chemistry and nanomedicine by rationally designing and fabricating versatile intelligent and multifunctional ultrasound-responsive nanosystems/nanoplatforms to solve the critical issues of traditional microbubbles and routine nanosystems, which is herein classified as "ultrasound-responsive nanomedicine". This review discusses and clarifies the intrinsic chemistry (e.g., material chemistry, surface chemistry, physiochemistry and biochemistry) and design principle of versatile nanosystems/nanoplatforms with unique ultrasound response not only for diagnostic bioimaging (single and/or multi-modality ultrasound imaging), but also for multiple ultrasound-triggered therapeutic applications. Based on the unique ultrasound features of high tissue-penetrating capability, non-invasiveness, easy accessibility and relatively mature apparatus, this review finally elucidates the unresolved critical issues/challenges and future clinical-translation potentials of this intriguing "ultrasound-responsive nanomedicine". (C) 2019 Elsevier Ltd. All rights reserved.