Studies are demonstrating additional benefits of multiple drug treatment in specific diseases. However, when a patient suffers multiple diseases, the lack of adequate clinical data on which to base a therapeutic attitude is baffling. The practitioner is forced to prescribe without a strong evidence base or to withhold medications for fear of doing more harm than good. In such circumstances, a prudent and drug sparing approach is to be preferred: a patient, not disease, oriented approach, using a few principles of rational prescribing: clear therapeutic objectives, prioritisation according to the severity of diseases, efficacy and safety of available therapies, therapeutic individualisation and monitoring, patient implication and attention to his/her desires and expectations.