If chemotherapy is to be effective against bone sarcoma, the cytotoxic agents must reach all tumor cells in effective quantities. Although many clinical trials include studies of the pharmacokinetics of these agents in blood or cerebrospinal fluid, there have been no accurate or widely applicable methods of determining whether chemotherapeutic agents reach all regions of a solid tumor. This review discusses the use of dynamic contrast-enhanced magnetic resonance imaging (DEMRI) to assess the microcirculation and interstitium of bone sarcoma. DEMRI studies provide a means of exploring leakage of contrast agent into tumor interstitium (extracellular extravascular spaces [EES]). In clinical observations of numerous series of patients with bone sarcoma, measures of contrast uptake (access) have convincingly demonstrated a relationship with measures and predictions of the tumor's response to preoperative chemotherapy. The results of these studies have indicated that greater access at the time of presentation, greater decrease in access during therapy, and low access at the completion of preoperative therapy correspond to better response and longer disease-free survival. Although questions remain about how these novel dynamic imaging methods can best be used to measure drug access noninvasively, we are optimistic that such measures can be developed to reflect the range of biological variation within and between naturally occurring solid tumors.