Previous studies on the work-family relationship have analyzed the influence of work-family conflict and work-family enrichment on an individuals’ lives, namely on their well-being and health. Besides, attempts have been made to analyze the influence of other aspects of the labor context on this relationship, such as job insecurity. However, few have analyzed this relationship and interaction from a longitudinal perspective. Thus, the main purpose of this study is to analyze the moderating role of job insecurity in the work-family relationship and the perceived health of 373 workers of a Portuguese bank, across time. The results showed a negative influence of work-family conflict on perceived health 5 years after. Also, job insecurity was found to offset the relationship between work-family enrichment and perceived health, acting as a buffer. This research allows for a better understanding of how job insecurity, a characteristic of modern-day employment, can impact workers' quality of life. This paper also refers to some practical implications, in addition to the limitations of the study, and presents suggestions for future research in this context.