This brief review focuses on reasons why myocardial perfusion imaging (MPI) SPECT defects may appear "fixed" (rest vs stress). A combination of technical and physiology factors are responsible in most cases and are discussed. Perhaps the major reason defects will appear fixed is that there is no absolute quantitative measurement of myocardial blood flow (MBF, rest and stress) with which to assess the magnitude and potential direction of change in the defect vs reference zone with stress. Cardiac PET MPI provides absolute measurements of MBF required to understand the clinical significance of the SPECT "fixed" defect and are highlighted. Emphasis is given to use of the actual MBF measurements though indexing stress MBF to that of truly normal subjects (RFR or FFRPET) will prove useful in recognition of multi-vessel CAD. The availability of 18F flurpiridaz for clinical use is likely to encourage more widespread adoption of cardiac PET MPI for evaluation of patients with known or suspected CAD.