We summarize a new approach to neuromodulator detection that provides colocalized detection of dopamine, serotonin, and norepinephrine at subsecond timescales and promises to provide submillisecond estimates of the same. The methodology, elastic net electrochemistry, is used to estimate dopamine and serotonin in the striatum of conscious human subjects during active decision-making. We show a proof-of-principle example of the same method working on commercially available depth electrodes in common use for epilepsy monitoring and neurosurgical planning in humans, which further promises to make such electrodes sources of fast neuromodulator information never before available in human subjects. We discuss the implications of this methodology for making direct tests in humans of the computations carried by these three important neuromodulatory systems. The methods also promise great utility in model organisms, but this chapter focuses on the possibilities for human use.