Stimulus-responsive systems have demonstrated for some time now significant advantages for the therapeutic and imaging fields. Nevertheless, this last decade was marked by the emergence of innovative concepts, opening new avenues of investigation. Since the field's inception, the driving force for the development of responsive materials has been motivated by the potential to modulate remotely a therapeutic or diagnostic action, with precise spatial and temporal control via externally-applied physical stimuli, such as light, temperature, electric or magnetic fields. It became possible to actuate materials on-demand, by altering at distance molecular interactions at critical onset points, and to provide controlled and sustained drug delivery, drug activation, heat triggering and contrast enhancement. This special issue covers the latest achievements and prospects related to physically-triggered nanosystems for therapy and diagnosis. Notably, important progress has been achieved for precision nanomedicine in nucleic acid delivery and theranostics, described by Do et al [1] and Mohamed et al [2], respectively. Also, recent developments on nano/micro-motors as well as electric field-responsive nanosystems for controlled drug release deserve special attention, being overviewed by Srivastava et al [3] and Kolosnjaj-Tabi [4], respectively. We have also witnessed a new momentum in the field of physically-triggered nanosystems mainly due to the fast-forward progress in nanosystem design. Roca et al [5] shows how innovative synthesis routes revolutionized material combination, modular designs and shape possibilities. Dimers or multimers, multi-layered designs and exquisite shape control resulted in a new generation of materials featuring