Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has recently emerged as a promising method for both diagnosis and prognosis of cancer despite considerable variation in both the methods of data acquisition and analysis. Both to facilitate integration of results from multiple institutions and to ensure that the data reflect the underlying physiology as accurately as possible, several aspects of data acquisition should be taken into account when developing protocols for DCE-MRI regardless of how the data are analyzed. Among the relevant issues are the relationship between signal enhancement and contrast agent concentration, intra- or inter-patient variation in the blood contrast agent concentration as a function of time, requirements for spatial and temporal resolution, the impact of tumor heterogeneity, and the impact of patient motion during the study. This review considers these factors and, when possible, makes specific recommendations for addressing them experimentally.