The demographic shift towards an older population increases the public health burden. Two conditions, commonly occurring together, that contribute to this burden are hypertension and diabetes mellitus. Effective blood pressure (BP) control is particularly important in this patient population, with a recommended BP goal of <130/80 mmHg. Most of these patients will require treatment with a combination of antihypertensive agents to reach this goal. Polypharmacy can be defined as the use of two or more medications, and it is commonly seen in this patient population. The risks of polypharmacy and the potential for inappropriate therapy must be considered and balanced against the possible benefits of multiple drug therapies. An optimal approach to reducing the risks and maximizing the benefits of polypharmacy should include regular reviews of patients' medication lists, which can be changed to include, where appropriate, combination therapy and the use of single-pill combinations. Combination therapy can achieve greater BP reductions than monotherapy and can also enhance the safety and tolerability of pharmacotherapy. The safety and efficacy of numerous antihypertensive combinations in elderly patients have been demonstrated in a number of clinical trials. Single-pill formulations can simplify the medication regimen, and specific combinations can offer further benefits, such as enhanced reduction of macrovascular and microvascular complications, independent of BP reductions. Rational combination therapy can maximize BP control along with glycaemic control and help maximize the benefits of polypharmacy on outcomes in elderly patients with hypertension and co-morbid diabetes.