Hypertension affects one-third of all females in the United States, with the prevalence increasing over a female's lifespan. The approach to treating females with hypertension varies depending on a female's age, race, comorbidities, and whether she is of child-bearing age or pregnant. It is important to factor in the safety and effectiveness of antihypertensive medications across these populations of females. Blood pressure target goals are the same in females as in males regardless of comorbidities or stage of life, with the exception of those females who are pregnant. Recommendations for antihypertensive medication do not differ between females and males based on disease state or stage of life, with the exception of females who are pregnant, breastfeeding, or of child-bearing age. Multiple guidelines recommend avoiding renin-angiotensin system blockers during pregnancy and suggest balancing the risk versus benefit in females of child-bearing age. Further, multiple guidelines provide race-based therapy recommendations for the use of calcium channel blockers and thiazide diuretics in black versus nonblack patients, irrespective of sex. Future research is needed to evaluate whether there are sex differences relative to blood pressure and cardiovascular event-lowering relative to specific antihypertensive medications with a focus on pharmacogenomic differences.