For the evaluation of biological processes using radioisotopes, there are two competing technologies: single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Both are tomographic techniques that enable 3D localization and can be combined with CT for hybrid imaging. PET-CT has clear technical superiority including superior resolution, speed and quantitative capability. SPECT-CT currently has greater accessibility, lower cost and availability of a wider range of approved radiotracers. However, the past decade has seen dramatic growth in PET-CT with decreasing costs and development of an increasing array of PET tracers that can substitute existing SPECT applications. PET-CT is also changing the paradigm of imaging from lesion measurement to lesion characterization and target quantification, supporting a new era of personalized cancer therapy. The efficiency and cost savings associated with improved diagnosis and clinical decision-making provided by PET-CT make a cogent argument for it becoming the dominant molecular technique in oncology.