An integral step in clinical trial design is the identification of the intervention to be studied and what, if any, control group will serve for comparison. Similar to the study endpoints, the interventions and controls of the trial are originally stipulated in the primary research question, further defining its importance. Although presented in a stepwise format, the precise definition of intervention and control is inherently closely linked to the establishment of the endpoints and so the processes may occur more concurrently. The time spent early in the design phase defining the intervention and controls up front is essential to the subsequent conduct and success of the trial. The intervention needs to be relevant to the disease being studied, needs to be supported by sufficient equipoise regarding its role in treatment, and needs to potentially offer something better than the current standard, especially if it incurs greater risk. Finally, the proper control group needs to be selected to make the comparison and conclusions believable, applicable, and generalizable. If these criteria are reached, then you are another step closer to the critical new knowledge that will positively impact clinical practice and improve patient outcomes.