Meaning in life is a core component of human experience, and it plays a relevant role in the promotion of mental, social and physical well-being, as well as in the successful adaptation to adverse conditions, including chronic and progressive diseases. This paper provides an overview of the most recent conceptualizations of meaning in the psychological domain, specifically addressing its tripartite structure, encompassing the facets of coherence, significance and purpose. Empirical evidence will be summarized concerning the role of social relationships and self-transcendence as primary sources of meaning in life. Research findings highlighting the role of meaning as a core component of mental health,and as a resource in adaptively managing illness consequences on daily functioning and life goals will be also reported. Current research gaps and future directions for theoretical and empirical advancements will be outlined