Non-invasive control of the drug molecules accessibility is a key issue in improving diagnostic and therapeutic procedures. Some studies have explored the spatiotemporal control by light as a peripheral stimulus. Phototriggered drug delivery systems (PTDDSs) have received interest in the past decade among biological researchers due to their capability the control drug release. To this end, a wide range of phototrigger molecular structures participated in the DDSs to serve additional efficiency and a high-conversion release of active fragments under light irradiation. Up to now, several categories of PTDDSs have been extended to upgrade the performance of controlled delivery of therapeutic agents based on well-known phototrigger molecular structures like o-nitrobenzyl, coumarinyl, anthracenyl, quinolinyl, o-hydroxycinnamate and hydroxyphenacyl, where either of one endows an exclusive feature and distinct mechanistic approach. This review conveys the design, photochemical properties and essential mechanism of the most important phototriggered structures for the release of single and dual (similar or different) active molecules that have the ability to quickly reason of the large variety of dynamic biological phenomena for biomedical applications like photo-regulated drug release, synergistic outcomes, real-time monitoring, and biocompatibility potential.