The widespread and successful use of radiopharmaceuticals in diagnosis, treatment, and therapeutic monitoring of cancer and other ailments has spawned significant literature. The transition from untargeted to targeted radiopharmaceuticals reflects the various stages of design and development. Targeted radiopharmaceuticals bind to specific biomarkers, get fixed, and highlight the disease site. A new subset of radioprobes, the bioresponsive radiopharmaceuticals, has been developed in recent years. These probes generally benefit from signal enhancement after undergoing molecular changes due to the fluctuations in the environment (pH, redox, or enzymatic activity) at the site of interest. This review presents a comprehensive overview of bioresponsive radioimaging probes covering the basis, application, and scope of development.