The concept of workload describes the relationship between a human operator and the momentary task demands. Conventionally workload is defined as a subjective state of the operator that can be reported with use of psychometric scales. The effects of workload on performance and reaction times yield important “objective” sources of information. Signal detection theory provides us with a useful framework within which we can interpret the effects of workload on discriminability (d’) and measures of response bias (β, corresponding to the likelihood ratios of the noise and noise plus signal functions at the criterion). Modern brain imaging techniques can be employed to determine the effects of workload on task-related neural responses in specific regions of the human brain. We describe a neurocognitive approach to research on the effects of workload in simulated (laboratory) and real (field) experiments. The findings suggest that functional brain imaging can provide important new insights into the way operators perform in challenging tasks.