All patient subpopulations are inherently “special” based on their unique constellations of clinical and demographic features that moderate and mediate treatment outcomes. This chapter will focus on diversity across distinct clinical subpopulations for which moderating or mediating factors do not simply provide information about the likelihood of a favorable drug response, but more specifically identify the need to adjust medication dosages or regimens, or favor certain medications over others based on evidence for safe and effective use in a particular patient group. Chronological age and biological sex assignment rarely in themselves signal the need for dosage adjustments, although associated features (e.g., diminished hepatic or renal function; pregnancy, premenstrual mood disturbances) may bear on a select evidence base for a given subpopulation. Metabolic (e.g., CYP450) enzymes also can vary by race, gender, age, and genetic polymorphisms, as noted in Chapter 8.