The purpose of a phase II trial is to determine whether an anticancer agent is sufficiently promising to take forward to a definitive, randomized, phase III study. Traditional phase II trials use tumor response as an end point, defined as a 50% or greater decrease in tumor size. Anticancer botanicals and supplements are unlikely to bring about rapid tumor regression, even if they do extend survival. Accordingly, response needs to be defined in terms of survival, such as being progression-free at 6 months. Such an approach requires historical data on the expected survival rate in the absence of the botanical or supplement. We present a simple phase II design for botanicals and supplements that is based on appropriate use of historical data, incorporating adjustment for both sampling variation and case mix. The basic principle is to use a historical cohort to generate a statistical prediction model, use this to predict results of patients in the phase II study, and then compare the predictions to the observed results. Such a design asks whether patients treated by the new agent are doing better than expected; if so, this suggests that the agent should be tested further in phase III trials.