The aim of this study is to present dilemmas associated with the use of drugs improving cognitive functions in the elderly with medical comorbidities. Considering high incidence of multiple pathology present in the elderly, dementia, being one of the most serious medical problems at this stage of life, rarely appears as an isolated condition and most often coexists with other diseases. Treatment of dementia is usually combined with therapy of other disease entities, thus inducing an increased risk of drug interactions and adverse effects. The risk of such phenomena increases further due to altered pharmacokinetics, resulting from worse distribution of drugs in the body and age-associated multi-organ failure, which in turn may lead to impaired metabolism and elimination of drugs. Among several acetylcholinesterase inhibitors used in the treatment of dementia, interactions concern most often donepezil, due to its hepatic metabolism involving the cytochrome P450, which also plays an important role in the metabolism of many other agents used in the management of other diseases affecting the elderly. Contraindications for the use of acetylcholinesterase inhibitors include mainly severe liver failure, sick sinus syndrome, arrhythmias and conduction disorders, active peptic ulcer within the stomach or duodenum, conditions hindering flow of urine, convulsions/seizures, and bronchial asthma or COPD. Adverse effects of medications concern a considerable proportion of patients, and for some of them this may be a contraindication for continuation of the therapy. Unfortunately, the issue of drug interactions and adverse effects is often underestimated in the treatment of elderly patients with dementia.