Molecular beacons are essentially all probes that illuminate particular cellular target or cells with similar characteristics. In this review we focus on those molecular beacons that use near-infrared fluorescence imaging (NIRF-I) to identify the unique cellular and metabolic markers characteristic of cancer. They employ various delivery and activation pathways, selectively or specifically targeting proliferating and immortal cancer cells. These beacons can either be used in an imaging step separate from therapy or they can intimately connect these two steps into a single process. Matching cancer therapy to NIRF-I is photodynamic therapy (PDT) that uses the light-triggered phototoxic properties of some porphyrin-based dyes. Guided by beacon's restored fluorescence, the PDT laser could be focused on affected sites, killing the cancer cells using the enhanced photoactivity of the same beacon. Or vice versaa—the restored fluorescence from the cleaved beacon could be used as an indication of the beacon's own therapeutic success, imaging the post-PDT apoptotic cells.