Malignant solid tumors have been traditionally treated utilizing cytotoxic chemotherapies, which work against rapidly multiplying tumors. The current response evaluation in solid tumor is based on the Response Evaluation Criteria in Solid Tumors (RECIST). This method relies mainly on computerized tomography (CT scans) and other imaging modalities by which the diameter of tumors is taken into consideration to assess response to therapy. Recent years have witnessed the introduction of a series of new signal transduction inhibitors in the management of metastatic RCC. Stable disease (SD) is more frequently seen with morphologic lesion changes such as, change in attenuation, pattern of intratumoral enhancement / necrosis and cavitation, all of which pose a challenge for the investigator in the accurate assessment of response to therapy. This article attempts to introduce the reader to various alternate concepts of monitoring response following biologic therapy and offers a detailed analysis of a few lesions.