This article reviews important considerations for researchers who are designing adaptive clinical trials. These differ from conventional clinical trials because they allow and even enforce continual modifications to key components of trial design while data are being collected. This innovative approach has the potential to reduce resource use, decrease time to trial completion, limit allocation of participants to inferior interventions, and improve the likelihood that trial results will be scientifically or clinically relevant. Adaptive designs have mostly been used in trials evaluating drugs, but their use is spreading. The US Food and Drug Administration recently issued guidance on adaptive trial designs, which highlighted general principles and different types of adaptive clinical trials but did not provide concrete guidance about important considerations in designing such trials. Decisions to adapt a trial are not arbitrary; they are based on decision rules that have been rigorously examined via statistical simulations before the first trial participant is enrolled. The authors review important characteristics of adaptive trials and common types of study modifications and provide a practical guide, illustrated with a case study, to aid investigators who are planning an adaptive clinical trial.