There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug events. Key considerations for older adults include: the use of loop diuretics, mineralocorticoid receptor antagonists (MRAs), and sodium glucose co-transporter-2 (SGLT2) inhibitors for most; angiotensin receptor blockers/ angiotensin receptor-neprilysin inhibitors (ARB/ARNIs) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) as add-on therapies for some, though risk of geriatric conditions such as falls, malnutrition, and/or sarcopenia must be considered; and beta blockers for a smaller subset of patients (with consideration of deprescribing for some, though data are lacking on this approach). Naturally, when making clinical decisions for older adults with cardiovascular disease, it is critical to consider the complexity of their conditions, including cognitive and physical function and social and environmental factors, and ensure alignment of care plans with the patient's health goals and priorities.