(1) Background: The increasing use of e-cigarettes/vaping in children and adolescents has been recognised as a global health concern. We aim to explore the Knowledge, Attitude, and Practice of General Practitioners (GPs) in Sydney regarding the use of e-cigarettes in children and adolescents and identify the barriers to addressing this issue. (2) Methods: This pilot study was a cross-sectional study conducted using an electronic questionnaire with a Likert scale and free-text responses. (3) Results: Fifty-three GPs participated in the study (male = 24 and female = 29) with a mean age of 50 ± 5.5 years. There was strong agreement (mean 4.5) about respiratory adverse effects and addictive potential. However, there was less awareness of cardiac side effects and the occurrence of burns. There is a lack of conversation about e-cigarettes in GP practice and a deficit of confidence in GPs regarding managing e-cigarette use in children and adolescents. (4) Conclusions: Our pilot study has shown that GPs are somewhat knowledgeable about the potential adverse effects of the use of e-cigarettes in children and adolescents, though there is a lack of knowledge of the complete spectrum of adverse effects and more importantly, there is a paucity of a structured approach to discuss the use of e-cigarettes with children and adolescents, and there is a low level of confidence in addressing these issues. There is a need for educational interventions for GPs to increase awareness of the potential adverse effects of using e-cigarettes and build confidence in providing management to children and adolescents regarding the use of e-cigarettes.