Purpose – The purpose of this paper is to examine whether work-family (WF) interference functions as an explaining mechanism in the link between work-family culture and well-being, hereby distinguishing between a negative and a positive process. The negative, energy depleting process initiates from a hindrance work-family culture and ends up to burnout through the experience of work-family conflict. The positive, motivation generating process initiates from a supportive work-family culture and ends up to work engagement through work-family enrichment. Design/methodology/approach – The paper employs a quantitative study among employees from three different organizations (n=516). Findings – Work-family conflict fully mediates the relationship between a hindrance WF-culture and the exhaustion dimension of burnout and partially mediates the relationship between a hindrance WF-culture and the cynicism dimension of burnout. With regard to the mediational role of work-family enrichment the results also confirm the paper's hypothesis. Work-family enrichment partially mediates the relationship between a supportive WF-culture and work engagement. Interestingly, analyses of some alternative mediational paths reveal some additional findings. Specifically, a supportive work-family culture relates to work engagement through the perception of less work-family conflict. Moreover, a supportive culture is also related to less feelings of burnout through work-family enrichment. Originality/value – The study shows that it pays off to invest in a supportive work-family culture because such a culture contributes to work engagement and in the same time helps to prevent burnout.