Menopausal hormone therapy (MHT) is the best treatment to alleviate the climacteric symptoms and improve the quality of life in symptomatic postmenopausal women. MHT has long-term benefits for osteoporosis, possibly on cardiovascular health and cognitive disorders, can benefit depression, and decrease colon cancer risk. In women with premature ovarian insufficiency, MHT is recommended up to the average age of menopause, but contraindications exist in certain clinical conditions. The clinical impact of the various types of MHT needs to be known. Vaginal administration of estrogens or dehydroepiandrosterone is devoid of systemic risk and can be prescribed without contraindication (except in women on aromatase inhibitors). Chronic auto-immune, pulmonary and neurodegenerative diseases are a burden for women, frequently worsening after menopause. Osteoporosis is frequent, as well as fatigue and depression. Healthcare providers are frequently hesitant to prescribe MHT in women with chronic disease, by fear of side-effects. The impact of MHT on many diseases is still controversial. Here, we analyze the information available in favor or not of the use of MHT in several auto-immune diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s disease, multiple sclerosis, and systemic sclerosis), inflammatory bowel diseases, chronic pulmonary diseases, and neurodegenerative diseases. Although in most of these chronic diseases, estrogens can have benefits on the symptoms of menopause and the course of the disease itself, each patient exhibits a specific clinical situation that needs an individualization of MHT.