This chapter discusses how vulnerability takes on contrasting and ambivalent meanings when approached at different levels. More specifically, the chapter stresses that institutional approaches do not necessarily align with the perceptions and experiences of those who are defined as vulnerable. Over the last several decades, scientific knowledge, and technical and medical measures have supported the development of the prevention and management of vulnerability. However, despite social and public health interventions, vulnerability reduction remains unequal across social groups. Starting from this mismatch, this chapter focuses on how individuals in vulnerable circumstances develop their own strategies and meanings in a context of adversity, along but also against collective definitions of and responses to vulnerability. Based on research conducted in LIVES on health trajectories, the first section of the chapter shows the importance of paying attention to various understandings of vulnerability while stressing their situated character. The second section illustrates the argument in greater depth by using elements from a qualitative study on the experience of HIV-infected women’s trajectories to highlight contradictions between their own understandings of vulnerability and its medical framing. In conclusion, the chapter stresses the importance to policy making of defining vulnerability based on people’ s needs and their own assessments.