Radiographic imaging has deep roots as a surrogate for efficacy in guiding decisions in therapy development in lymphoma. Nodal lymphomas are generally easy to measure in two dimensions and frequently shrink promptly when exposed to therapies that result in long-term clinical usefulness. New therapies in lymphoma are still required to induce radiographic response to be considered useful in a paradigm dating back at least to chest roentgenograms and Hodgkin's lymphoma (HL). This paradigm will soon be challenged by new therapeutic strategies under development, but creative imaging approaches can still guide such development.