Extensive research has been conducted to examine the relationship between experience of pleasure (hedonic well-being) and experience of meaning (eudaimonic well-being). A general consensus is that they are both important in well-being and that they are related but distinct. However, recent studies linking well-being and gene expressions suggest that eudaimonic well-being is more associated with better gene regulatory programs than hedonic well-being. My program of research extends this finding by showing that orientation toward, not actual experience of, pleasure vs. meaning has also distinct well-being outcomes. Specifically, I will present evidence that orientation toward meaning is more associated with various well-being indices including gene expressions than orientation toward pleasure. Our recent study reveals that orientation toward meaning showed down-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving decreased expression of proinflammatory genes and increased expression of genes involved in antibody synthesis and type I IFN response. I will also show that the advantage of meaning orientation over pleasure orientation becomes larger with age.