Neuromodulation is "the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body". It is carried out to normalize – or modulate – nervous tissue function. Neuromodulation is an evolving therapy that can involve a range of electromagnetic stimuli such as a magnetic field (rTMS), an electric current, or a drug instilled directly in the subdural space (intrathecal drug delivery). Emerging applications involve targeted introduction of genes or gene regulators and light (optogenetics), and by 2014, these had been at minimum demonstrated in mammalian models, or first-in-human data had been acquired. The most clinical experience has been with electrical stimulation.

Neuromodulation, whether electrical or magnetic, employs the body's natural biological response by stimulating nerve cell activity that can influence populations of nerves by releasing transmitters, such as dopamine, or other chemical messengers such as the peptide Substance P, that can modulate the excitability and firing patterns of neural circuits. There may also be more direct electrophysiological effects on neural membranes as the mechanism of action of electrical interaction with neural elements. The end effect is a "normalization" of a neural network function from its perturbed state. Presumed mechanisms of action for neurostimulation include depolarizing blockade, stochastic normalization of neural firing, axonal blockade, reduction of neural firing keratosis, and suppression of neural network oscillations. A recent review (2024) has identified relevant etiological hypotheses of non-invasive neuromodulation in different techniques. Data analysis revealed that mitochondrial activity seems to play a central role in different techniques. Analysis of the mother-fetus neurocognitive model provided insights into the conditions of natural neuromodulation of the fetal nervous system during pregnancy. According to this position, the electromagnetic properties of the mother's heart and its interaction with her own and the fetal nervous system ensure the balanced development of the embryo's nervous system and guarantee the development of the correct architecture of the nervous system with the necessary cognitive functions corresponding to the ecological context and the qualities that make human beings unique. Based on these results, the article suggested the hypothesis of the origin of neurostimulation during gestation. Although the exact mechanisms of neurostimulation are not known, the empirical effectiveness has led to considerable application clinically.

Existing and emerging neuromodulation treatments also include application in medication-resistant epilepsy, chronic head pain conditions, and functional therapy ranging from bladder and bowel or respiratory control to improvement of sensory deficits, such as hearing (cochlear implants and auditory brainstem implants) and vision (retinal implants). Technical improvements include a trend toward minimally invasive (or noninvasive) systems; as well as smaller, more sophisticated devices that may have automated feedback control, and conditional compatibility with magnetic resonance imaging.

Neuromodulation therapy has been investigated for other chronic conditions, such as Alzheimer's disease, depression, chronic pain, and as an adjunctive treatment in recovery from stroke.

Electrical stimulation using implantable devices came into modern usage in the 1980s and its techniques and applications have continued to develop and expand. These are methods where an operation is required to position an electrode. The stimulator, with the battery, similar to a pacemaker, may also be implanted, or may remain outside the body.

In general, neuromodulation systems deliver electrical currents and typically consist of the following components: An epidural, subdural or parenchymal electrode placed via minimally invasive needle techniques (so-called percutaneous leads) or an open surgical exposure to the target (surgical "paddle" or "grid" electrodes), or stereotactic implants for the central nervous system, and an implanted pulse generator (IPG). Depending on the distance from the electrode access point an extension cable may also be added into the system. The IPG can have either a non-rechargeable battery needing replacement every 2–5 years (depending on stimulation parameters) or a rechargeable battery that is replenished via an external inductive charging system.

Although most systems operate via delivery of a constant train of stimulation, there is now the advent of so-called "feed-forward" stimulation where the device's activation is contingent on a physiological event, such as an epileptic seizure. In this circumstance, the device is activated and delivers a desynchronizing pulse to the cortical area that is undergoing an epileptic seizure. This concept of feed-forward stimulation will likely become more prevalent as physiological markers of targeted diseases and neural disorders are discovered and verified. The on-demand stimulation may contribute to longer battery life, if sensing and signal-processing demands of the system are sufficiently power-efficient. New electrode designs could yield more efficient and precise stimulation, requiring less current and minimizing unwanted side-stimulation. In addition, to overcome the challenge of preventing lead migration in areas of the body that are subject to motion such as turning and bending, researchers are exploring developing small stimulation systems that are recharged wirelessly rather than through an electrical lead.

Spinal cord stimulation is a form of invasive neuromodulation therapy in common use since the 1980s. Its principal use is as a reversible, non-pharmacological therapy for chronic pain management that delivers mild electrical pulses to the spinal cord. In patients who experience pain reduction of 50 percent or more during a temporary trial, a permanent implant may be offered in which, as with a cardiac pacemaker, an implantable pulse generator about the size of a stopwatch is placed under the skin on the trunk. It delivers mild impulses along slender electrical leads leading to small electrical contacts, about the size of a grain of rice, at the area of the spine to be stimulated.