This chapter reviews the implications of the estimand framework on various clinical trial designs. It details the unique estimand considerations for non-inferiority and equivalence trials, focusing on strategies for addressing intercurrent events. It also explores the application of the estimand framework in adaptive and master protocol designs, highlighting the need for careful planning and consideration of treatment-related and population-specific intercurrent events. In multiregional clinical trials, the estimand framework formalizes the treatment effect assessment in the overall population and the specific regional populations. This chapter also discusses different strategies addressing treatment switching in oncology trials for estimating overall survival benefits. Finally, this chapter reviews decentralized clinical trials, emphasizing the impact of decentralization on estimands and the estimator’s properties, along with the potential for targeting novel estimands through patient-centric measures. Different case studies illustrate practical applications of the estimand framework in various trial designs, demonstrating its flexibility and utility. This chapter concludes by highlighting the evolving nature of clinical trial designs and the importance of the estimand framework in improving trial design, conduct, and analysis.