Combined structure-function approach utilizing the fusion of functional and anatomical modalities for more precise localization has been a major innovation of recent times in the arena of medical imaging. This approach is likely to make a major impact on the diagnosis and management of various benign and malignant disorders. The SPECT/CT and the PET/CT imaging systems are the two proof-of-principle examples that clearly depict the power of this approach. The advantages are particularly evident in patients with cancer where fused image obtained by the combination of functional data from PET/SPECT with high-resolution anatomical detail from a multi-slice CT scanner provides useful anatomical and functional information to detect, diagnose, characterize, or monitor tumors before and after therapeutic intervention and guide biopsies or surgical interventions. The approach is likely to be pivotal to optimize individualized treatment planning for several malignancies. Based upon available evidence at this point, the relatively established clinical applications of hybrid SPECT-CT in oncology include (a) lymphoscintigraphy, (b) bone imaging and (c) octreotide scintigraphy for investigating neuroendocrine tumors. The other emerging situations where it holds considerable potential include: patient specific dosimetry and estimation of organ residence time for planning of radionuclide therapy planning, as well as evaluation of malignancies where the role of FDG-PET imaging is limited (e.g. prostate cancer using capromab pendetide and brain tumors). Combined PET/CT imaging, on the other hand, has been integrated into the management of majority of the malignancies because it offers advantages in a large number of decision making steps in oncological practice including staging of the disease, therapy planning and monitoring treatment response and is considered as the ‘one stop shop’ investigation for the management of these patients. In this mini-review we discuss the impact of SPECT-CT and PET-CT imaging approaches which are becoming increasingly important for therapeutic decision making in the era of personalized medicine.