Tinnitus is the perception of sound in the absence of a corresponding acoustic stimulus. Classical neuromodulation—which consists of applying electrical or magnetic stimuli to the nervous system to directly modulate ongoing brain activity—can temporarily disrupt these phantom sensations but has not been successful as a causal treatment. Recently, however, an exciting novel neuromodulation technique was developed in which stimulation of a cranial nerve was paired with simultaneous presentation of tones, demonstrating that it reverses a tinnitus percept in noise-exposed rats. Pairing cranial nerve stimulation with another therapy can drive activation of nuclei that are associated with modulating plasticity. Repeatedly pairing brief stimulation with sensory or motor events drives robust, event-specific plasticity in neural circuits. To determine whether this treatment approach could be effective in humans, we delivered a similar therapy in patients with chronic tinnitus who were unresponsive to previous therapies. We developed two lines of research to this end. In the first approach, we stimulated the vagus nerve paired with tones, while for the second we stimulated the trigeminal nerve paired with tones. Both treatment approaches seem to well-tolerated and adverse effects were mild. Both vagus and trigeminal nerve stimulation seem to be able to suppress tinnitus, however show a different long-term effect. These results offer concrete evidence that cranial nerve stimulation paired with tones can direct therapeutic neural plasticity.