<p>Chimeric Antigen Receptor T-cell (CAR-T) therapy has unprecedentedly improved outcomes for patients with relapsed or refractory B-cell malignancies, offering the prospect of survival to patients with otherwise poor prognoses. Despite these advances, CAR-T therapy presents multiple challenges as it is not always effective, possibly harmful with severe, potentially life-threatening side effects, resource-demanding and expensive. Furthermore, patient selection and prioritization (e.g., in case of limited hospital or manufacturing capacity) is complex, as no standardized criteria exist and reliable predictive tools to determine individual outcomes upfront are still being developed. This creates ethical challenges that healthcare professionals need to navigate in order to provide good care to their patients, and that may be a cause of moral distress, which may affect their well-being. Addressing these ethical challenges is therefore crucial for both patients and healthcare professionals. Yet, up until now, they are hardly explored in the context of CAR-T treatment. We will therefore present a preliminary overview of current ethical challenges in CAR-T treatment in clinical practice, based on our experiences as clinicians and clinical ethicists. Furthermore, we will address how these challenges may be navigated in clinical practice, proposing clinical ethics support, particularly through moral case deliberation. As the application of CAR-T therapy is increasing, it is expected that more healthcare professionals will encounter ethical challenges and this warrants adequate support to enhance quality of patient care while also contributing to the well-being of healthcare professionals.</p>