In a four-wave, longitudinal study (N = 323), we tested the relationships between five positive dispositions—mindfulness, self-compassion, gratitude, hedonism, and eudaimonism—and time-varying negative affect, positive affect, life satisfaction, and meaning in life. These relationships were tested while controlling for the ups and downs in life across three months, operationalized as the effects, for a respondent, of having experienced more frequent and intense positive and negative events compared to other individuals in the sample (inter-individual variation) and of having experienced more frequent and intense positive and negative events than usual for that person (intra-individual variation). We also tested the interactive effects between each disposition and intra-individual variation in the frequency and intensity of negative and positive events on well-being variables. Results, obtained through multilevel models with repeated observations nested in individuals, showed that each disposition had specific associations with well-being indicators, although stronger effects were detected for eudaimonism and, especially, self-compassion. Moderation analyses showed that: mindfulness and self-compassion buffered intra-individual variation in negative events; people scoring higher on hedonism, eudaimonism, and self-compassion showed less need to rely on positive events to experience positive emotions; experiencing a negative event that was more intense than usual was associated with higher meaning in life for people with high levels of eudaimonism. Overall, findings suggest that mindfulness, self-compassion, gratitude, hedonism, and eudaimonism build well-being through different channels. Positive interventions could benefit from mixing these healthy functioning strategies and considering their roles in reactions to events.