Quantitative analysis can improve the sensitivity and specificity of single photon emission tomography (SPET) procedures, as well as reduce inter- and intraobserver variabilities. Quantification of the radioactivity distribution is the ultimate goal of SPET. In this review we consider the basic requirements for an optimum three-dimensional reconstruction of the radionuclide distribution to enable quantification. Attenuation and scatter correction as well as varying resolution are the major problems. In the older SPET systems quantification was hampered by the lack of system sensitivity and sufficient computer power. Therefore, the imaging system was often assumed to be shift invariant and linear and the attenuation throughout the object uniform. More sophisticated solutions have been proposed and with more or less success implemented, but not for application in daily practice. Knowledge (measurement) of the attenuation is often required. New generation SPET systems employing multi-detectors and super minicomputers will ease the implementation of these solutions.