Second generation antihistamines have been commonly used in treatment of allergic disorders for decades, especially in allergic rhinitis, urticaria, atopic dermatitis and allergic conjunctivitis. They are frequently used in everyday clinical practice, mainly because of high efficacy and excellent safety profile. In allergic disorders we use the potency of antihistamines to bind to histamine receptors, while in other diseases we use them because of their possible anti‑inflammatory mechanisms. Antihistamines are usually administered in monotherapy, however, in some cases we combine them with other agents. Certain antihistamines drugs have similar mechanisms of action, however, we can find distinct differences between the drugs. This is the reason why in case of no significant clinical improvement it is possible to add one antihistamine drug to another in order to enhance efficacy, it is also possible to increase a single therapeutic dose even up to four times. These observations based on clinical experience are the reason why it is necessary to conduct further studies on schemes of antihistamines drugs’ administration. In the article frequently used drugs are presented, especially their clinical efficacy and safety. Results of chosen clinical trials are also reported. Some controversial topics are mentioned, especially combined use of certain drugs and the possibility of applying higher daily doses.