Background: Lack of education and training in palliative care has been described to be one of the most important barriers to pediatric palliative care implementation. Objective: To examine what factors determine the degree of knowledge and level of comfort Mexican pediatricians have providing pediatric palliative care. Methods: A questionnaire that assessed palliative care concepts was developed and applied online to Mexican pediatricians, both generalists and specialists. Results: A total of 242 pediatricians responded. The majority had not received palliative care education (92.6%) and felt uncomfortable discussing palliative needs with patients and families (92.1%). The mean score of the questionnaire was 6.8 (+1.4) of 10 correct answers. Knowledge in palliative care was associated with exposure to oncologic patients (P ¼ .01) and previous palliative care education (P ¼ .02) but inversely related to the pediatrician's age (P ¼ .01). Comfort addressing patient's palliative care needs was associated with knowledge in palliative care (P < .01), exposure to oncologic patients (P ¼ .03), and previous education in palliative care (P ¼ .02). Conclusions: Although Mexican pediatricians have basic knowledge of palliative care concepts, they do not feel comfortable addressing palliative care needs, suggesting that the main barrier for implementing palliative care is not the lack of knowledge but rather feeling uncomfortable when addressing these issues with patients and families. Educational programs should incorporate strategies that could help physicians develop comfort in approaching palliative care patients.