Interest in the study of vulnerability has experienced impressive growth across various disciplines. To contribute to this major but scattered development in the study of vulnerability, this article argues for a multidisciplinary life-course framework. This framework promotes a systemic and dynamic perspective focused on three complementary research directions: multidimensional, multilevel, and multidirectional. On the basis of this life course perspective, the authors also propose a definition of vulnerability as a dynamic process of stress and resources across various domains of life (i.e., work, family, health, migration, etc.), levels (i.e., person, group, collective), and time (i.e., long-term processes). The concept of vulnerability has recently captured a lot of attention. The topic emerged without a consensual definition, and paradoxically, its vagueness is likely part of its success. In this article, we show the richness of vulnerability as a concept used and that can be developed in a multi- and hopefully interdisciplinary effort. We define vulnerability in terms of the dynamics of stress and resources across the life course and illustrate its potential through the discussion of empirical examples, notably drawn from the Swiss National Centre of Competence in Research LIVES (www.lives-nccr.ch). On this basis, we propose three research directions aiming at developing a life-course framework for understanding the systemic and dynamic properties of vulnerability: multidimensional, multilevel, and multidirectional analyses.