In a number of applications, more than one drug has to be prescribed to achieve the desired therapeutic goal. Most often, it is the treatment of chronic diseases (like hypertension, type 2 diabetes mellitus, allergic asthma, but also chronic infectious diseases like tuberculosis or AIDS) which requires the combination of drugs with different mechanisms of action. Multimorbidity, often present in old age, increases the number of drug intakes per day while the ability to do so correctly declines. It appears thus plausible that a fixed combination of drugs, by decreasing the number of drug intakes per day, may lead to an improved compliance and eventually to an improvement of clinical endpoints. However, there is scarce evidence that this assumption is generally valid. For each of the above diseases the use of fixed combinations has to be evaluated separately with respect to an improvement in clinical endpoints as well as to an increased risk of adverse effects. Finally, the pharmacoeconomic aspect as to how the cost of fixed combinations compares to that of free combinations has to be taken into account.