This study aimed to develop and test a specific pattern of relationships between job demands, job resources and person-related factors on the one hand, and the three burnout dimensions on the other, among Dutch General Practitioners. In addition, we aimed to test whether gender differences exist in this regard. Based on several theoretical models such as the Job Demand-Control model and the Job Demands-Resources model of burnout as well as a review of burnout studies among physicians, we formulated a research model of burnout. The research questions were answered by means of self-report questionnaires using a full panel design with two waves. Cross-lagged panel analyses indicated that the causal direction of the relationships between demands, resources and person-related factors on the one hand, and burnout on the other is reciprocal. In addition, multi-sample analyses revealed that the pattern of relationships between job demands, job resources, person-related factors and burnout is different for men and women, although results are less clear at the second measurement point. Among other things, we recommend anticipating in a gender sensitive way on risk factors for burnout and motivation loss for young professionals by coaching and empowerment in vocational training.