Nonuniform attenuation, Compton scatter, and limited, spatially varying resolution degrade both the qualitative and quantitative nature of myocardial perfusion SPECT. Physicians must recognize and understand the effects of these factors on myocardial perfusion SPECT for optimal interpretation and use of this important imaging technique. Recent developments in the design and implementation of compensation algorithms and transmission-based imaging promise to provide clinically realistic solutions to these effects and provide the framework for truly quantitative imaging. This achievement should improve the diagnostic accuracy and cost-effectiveness of myocardial perfusion SPECT.