In the context of both research and clinical applications, Buddhist sources have inspired the theoretical and practical aspects of self-compassion as a construct and target of mental training. However, the Indo-Tibetan Buddhist traditions that most strongly emphasize the importance of compassion articulate it in ways that are incompatible with contemporary notions of self-compassion. This article examines these incompatibilities in terms of Indo-Tibetan Buddhist theory and practice. In theoretical terms, the articulation of compassion as centered on others (and not self) is explained in terms of its overall motivational purpose in Indo-Tibetan Buddhism. And in terms of Buddhist practices for cultivating compassion, incompatibilities in relation to motivation and phenomenological structure are examined. The possibility that self-compassion could be aligned with Buddhist notions of renunciation is next considered. The problems that arise in that attempted alignment motivate a concluding discussion about the ways that Buddhist insights about compassion suggest potentially useful ways of reconsidering contemporary conceptualizations and practices of self-compassion as a “skilful means” to address obstacles to cultivating a sincere motivation to strive for one’s own well-being.