Selecting appropriate psychiatric treatment can be challenging. It is particularly difficult in a group of patients burdened a priori by serious somatic conditions, i.e. kidney or liver failure, neurological diseases or glaucoma. When the use of antipsychotics is warranted, in addition to an adequate clinical effect profile, attention should also be paid to other features of the drug, such as its pharmacodynamic and pharmacokinetic properties and possible side effects. Almost all, with the exception of pimavanserin (not available in Poland), currently regis- tered antipsychotics are D2 receptor antagonists. Second-generation drugs additionally exert significant effects on serotonergic transmission, primarily by blocking 5HT2a receptors. On the other hand, modern third-generation antipsychotics, in addition to antagonism to D2 receptors, also exhibit partial agonism towards dopamine receptors, which allows modulation of dopaminergic transmission. This profile of interactions may influence the type of side effects. The purpose of this paper is to provide practical recommendations on the safety of antipsychotic drugs in groups of patients burdened by somatic conditions frequently encountered in clinical practice, i.e. renal failure, neurological conditions, including Parkinson’s disease and epilepsy, liver failure, prostatic proliferation and glaucoma. The paper represents a continuation of recommendations on the use of neuroleptics in patients with somatic diseases.