Traditional clinical trials of heart failure therapy have focused on fairly homogenous patient populations. Therefore, a pressing question is raised regarding whether it is appropriate to extrapolate findings from these trials to other groups, such as the elderly, women, and African Americans. Based on current knowledge, the differences among these groups should be acknowledged as subtle and represent a need for heightened clinical awareness and more vigorous investigation. These special populations, however, should receive medical therapy for heart failure that is consistent with the results from the major trials and is in accordance with published heart failure guidelines.