Major advances produced by healthcare research have resulted in an increasing number of drugs that may be used to modify disease expression and improve quality of life. These discoveries have been used by clinical pharmacologists as a basis to identify new drug candidates and to develop strategies for their optimal delivery to maximize benefit while simultaneously minimizing adverse events. Unfortunately, many of these studies do not include sufficient older persons in whom most of these drug therapy interventions are likely to apply. This article examines selected physiological, pathological and healthcare interventional changes with age that impact clinical drug studies and the decision to use drugs as therapy in older adults. Clinical examples are provided that illustrate confounders to the accomplishment of an ideal outcome, the improved quality of life that remains for this population.