One of the most important aspects for the evaluation of PET brain scans for research or clinical purposes is to be able to identify normal variants. This article reviews issues pertaining to the technical and neurophysiologic aspects of functional brain imaging that might alter “normal” activity as evaluated by PET imaging. This includes an evaluation of various types of radiopharmaceuticals that measure cerebral blood flow, cerebral metabolism, and neurotransmitter activity. The baseline state of the brain and normal activity patterns associated with cognitive, sensory, and emotional processes are discussed in this article. In addition, the changes in the brain that occur during the life span of normal individuals are also considered because there is a different “normal” for each stage of life.