<b>Introduction:</b> Primary chronic rhinosinusitis with nasal polyps (CRSwNP) is a severe, often uncontrolled disease whose pathomechanism involves type 2 inflammation (T2). Biologic drugs targeting interleukin 4 and 13 (dupilumab) receptors and blocking interleukin 5 (mepolizumab) have been approved for the treatment of the T2 endotype.<b>Aim:</b> Presentation of the authors' suggestions that guided the choice of an appropriate biologic agent when initiating qualification for the treatment of patients with CRSwNP, based on the authors' experience and data from the literature related to biologic therapy.<b>Materials and methods:</b> Patients with CRSwNP were qualified for biological treatment in accordance with the EPOS (European Position Paper on Rhinosinusitis) guidelines and the criteria of the B.156 drug program. The choice of an appropriate biologic was based on medical history data, such as the level of asthma control, presence of allergies, and the occurrence of N-ERD (nonsteroidal anti-inflammatory drug-exacerbated respiratory disease), as well as biomarker results: total IgE concentration and absolute blood eosinophil count.<b>Results:</b> The study included 43 patients (23 treated with mepolizumab, 20 treated with dupilumab). Groups of patients were comparable in terms of age, sex, number of sinonasal surgeries, prevalence of asthma, NSAIDs (non-steroidal anti-inflammatory drugs) sensitivity, atopy and initial SNOT-22 (Sinonasal Outcome Test-22), VAS (Visual Analog Scale), NPS (Nasal Polyp Score), and L-K score (Lund-Kennedy score). Eosinophilia total range was 250-1000 cells/microL. Baseline peripheral blood eosinophil count was significantly higher in the mepolizumab-treated group. In the dupilumab-treated group, increases in eosinophil counts up to 3500 cells/μl were observed during therapy; however, no patient developed clinical features of hypereosinophilic syndrome.<b>Conclusions:</b> When selecting a biologic drug for the treatment of CRSwNP, it is recommended to consider not only the values of available biomarkers, but also the degree of asthma control, the cumulative dose of oral corticosteroids (OCSs), the patient's age, and treatment convenience for the patient.