As a surrogate endpoint to measure response to treatment, Response Evaluation Criteria in Solid Tumors (RECIST) has been road-tested and found to correlate well with the Gold-Standard of Overall Survival. By offering, in essence, a surrogate estimation of tumor volume via unidimensional measurements, RECIST has provided not only an indicator of response to treatment, but also a common language in clinical trials of solid tumors. Increasingly, the use of targeted and immunotherapeutic agents has called into question the true value of RECIST, particularly in early clinical trials where go or no-go decision making is essential. Indeed, clinical trials are increasingly finding a lack of correlation with the use of RECIST to outcomes from early data. Here we explore measures of response beyond RECIST.