Ensuring population diversity in clinical trials is essential yet challenging and increasingly complex in the rare disease landscape. The unique challenges in clinical development for rare diseases include limited medical and scientific knowledge, poorly understood natural history data, sample size constraints, and a lack of drug development experience. This article will discuss the evolving regulatory framework for encouraging diversity in clinical trials, explore the unique challenges of applying recommendations within the rare disease landscape, and highlight sustainable solutions for overcoming challenges.     Medical Writing. 2025;34(1):42–45. https://doi.org/10.56012/chhh9584