The identification of a baseline or control state is fundamental for the interpretation of task- or stimulation-induced brain activation patterns. The conscious resting state in darkness is a frequently used, but ill-defined mental state. The mere transition from, for example, lid closed to lid open in darkness causes major changes in brain activity,which can mask or mimic a stimulus-dependent brain activation. Contradictory results of seemingly identical brain activation studies may be attributed to the choice of different baseline conditions. Therefore, control conditions that are closest to the stimulus or task condition should be used as baseline in most fMRI and PET studies rather than absolute relaxation in darkness and silence (REST).