Positron emission tomography (PET) with H2(15)O and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide noninvasive measurements of tumor blood flow. Both tools offer the ability to monitor the direct target of antiangiogenic treatment, and their use is increasingly being studied in trials evaluating such drugs. Antiangiogenic therapy offers great potential and, to an increasing extent, benefit for oncological patients in a variety of palliative and curative settings. Because this type of targeted therapy frequently results in consolidation of the tumor mass instead of regression, monitoring treatment response with the standard volumetric approach (Response Evaluation Criteria in Solid Tumors) leads to underestimation of the response rate. Monitoring direct targets of anticancer therapy might be superior to indirect size changes. In addition, measures of tumor blood flow contribute to a better understanding of tumor biology. This review shows that DCE-MRI and H2(15)O-PET provide reliable measures of tumor perfusion, provided that a certain level of standardization is applied. Heterogeneity in scan acquisition and data analysis complicates the interpretation of study results. Also, limitations inherent to both techniques must be considered when interpreting DCE-MRI and H2(15)O-PET results. This review focuses on the technical and physiological aspects of both techniques and aims to provide the essential information necessary to critically evaluate the use of DCE-MRI and H2(15)O-PET in an oncological setting.