Abstract This review discusses the development and recent advances of probes encapsulated by biologically localized embedding (PEBBLEs), and in particular the application of PEBBLEs as ion sensors. PEBBLEs allow for minimally intrusive sensing of ions in cellular environments due to their small size (20 to 600 nm in diameter) and protect the sensing elements (i.e. fluorescent dyes) by encapsulating them within an inert matrix. The selectivity and sensitivity of these nanosensors are comparable to those of macroscopic ion selective optodes, and electrodes, while the response time and absolute detection limit are significantly better. This paper discusses the principles guiding PEBBLE design including synthesis, characterization, diversification, the advantages and limitations of the sensors, cellular applications and future directions of PEBBLE research.