Postmenopausal women frequently suffer, in addition to their climacteric symptoms, from other diseases. Therefore, it is important to know when, in which form, and which dosage menopausal hormone therapy (MHT) may be prescribed with regard to the underlying chronic disease, and in which situations MHT is contraindicated. To minimize the risks of MHT in the presence of a chronic disease, the following basic rules should be kept in mind: If there is no absolute contraindication, MHT should be started within the "window of opportunity" (age <60 years or within 10 years of menopause). Transdermal administration is preferred; in the presence of most chronic diseases, a hepatic first pass effect is undesirable. The lowest efficient dosage should be selected because most side effects are dose dependent. In the presence of urogenital symptoms without systemic complaints, local vaginal treatment is chosen. Metabolically neutral progestagens, such as micronized progesterone, dydrogesterone and dienogest or non-oral administration of norethisterone acetate is preferred. Medroxyprogesterone acetate should be avoided. Cyclical fluctuations of hormone blood levels should be avoided. Angiopathies (e.g., in arterial hypertension, diabetes mellitus, lupus erythomatodes) are an absolute contraindication for MHT. In the absence of angiopathies, transdermal MHT might be prescribed in the presence of the same diseases after an extensive risk-benefit evaluation. As an example, transdermal MHT can be administered to a normotensive patient with well-treated and stable arterial hypertension and without arterial lesions. In case of doubt, the treating physician should be contacted regarding how to proceed further.