Personalised medicine is critical in managing allergic diseases, with the variety of second-generation antihistamines necessitating tailored approaches to individual patient needs. This encompasses considerations of age, pregnancy, breastfeeding, hepatic and renal failure, drug interactions, and aging. This paper synthesises current research and guidelines on the use of antihistamines across diverse clinical scenarios, paying special attention to paediatric allergy treatment, including safety profiles of first- and second-generation antihistamines, their use during pregnancy, breastfeeding, and interactions with other drugs, as well as considerations for elderly patients. Second-generation antihistamines are preferred for allergy treatment due to their safety, minimal adverse effects, and efficacy, with a strong recommendation against the use of first-generation antihistamines due to their potential to induce severe adverse reactions. Cetirizine, levocetirizine, and desloratadine are favoured in infants; whereas loratadine, rupatadine, and bilastine are recommended for preschoolers and older children. The safety of selected second-generation antihistamines during pregnancy (notably cetirizine, levocetirizine, desloratadine) and breastfeeding (notably loratadine, desloratadine, fexofenadine), in patients with renal failure and elderly patients (bilastine, desloratadine, fexofenadine), and patients with hepatic failure (bilastine, fexofenadine) is highlighted. The choice of secondgeneration antihistamines should be based on the patients’ individual needs and conditions to achieve optimal therapeutic outcomes and ensure safety, emphasising the importance of drug selection in varying clinical contexts.