Summary: Optimal management of chronic heart failure, despite the clear and structured message of guidelines, is a demanding task for the patient and remains a serious challenge for the physician. Selecting an appropriate drug combination must be followed by the continuous optimization of the therapy and should be aimed at obtaining the target doses of particular drugs, as recommended, based on existing evidence of a reduction in mortality. Coexisting multiple chronic disorders limit the ability to freely choose drugs or impose therapeutic regimens in accordance with relevant guidelines, thereby hindering a well-balanced decision. This paper synthetically summarizes the principles of treating heart failure in a patient with multiple diseases. Based on the current guidelines for the management of individual comorbidities, the essential steps that should be taken to maximally improve the prognosis, looking at the patient holistically through the eyes of an internist, are discussed. The most common mistakes made in the treatment of patients are listed, and some erroneous stereotypes in the approach to drugs used in heart failure with the coexistence of some chronic diseases are specified.