Closed-loop or intelligent neuromodulation allows adjustable, personalised neuromodulation which usually incorporates the recording of a biomarker, followed by implementation of an algori5 thm which decides the timing (when ?) and strength (how much ?) of stimulation. Closed-loop neuromodulation has been shown to have greater benefits compared to open-loop neuromodu lation, particularly for therapeutic applications such as pharmacoresistant epilepsy, movement disorders and potentially for psychological disorders such as depression or drug addiction. How ever, an important aspect of the technique is selection of an appropriate, preferably neural biomarker. Neurochemical sensing can provide high resolution biomarker monitoring for various neurological disorders as well as offer deeper insight into neurological mechanisms. The chemicals of interest being measured, could be ions such as potassium (K+), sodium (Na+ 12 ), calcium
(Ca2+), chloride (Cl−), hydrogen (H+ 13 ) or neurotransmitters such as dopamine, serotonin and glutamate. This review focusses on the different building blocks necessary for a neurochemi cal, closed-loop neuromodulation system including biomarkers, sensors and data processing algorithms. Furthermore, it also highlights the merits and drawbacks of using this biomarker modality.