Compassion science has been shaped and guided by Mahāyāna Buddhist conceptions of compassion, including the potential for compassion to be cultivated through contemplative practices and training. Despite these influences, important Buddhist perspectives and ideas about compassion are still underrepresented in the scientific literature. This Special Issue focuses on initiating a body of literature on skillful means, a foundational idea from Mahāyāna Buddhism pertaining to the enactment of compassion joined with wisdom. Arising from a seminal Think Tank centered around compassion and skillful means, scholars and trainers representing diverse perspectives were invited to contribute to a Special Issue introducing a variety of perspectives, insights, and approaches that may help to advance contemporary understanding, research, and training of compassion. This includes papers that examine skillful means within Buddhism and Christianity, empirical studies that draw on skillful means to motivate or frame tractable questions, theoretical papers that reflect on skillful means in relation to other topics in psychological science, and how common compassion practices may themselves serve as skillful means. Considered together, we believe the variety evident throughout this Special Issue highlights the potential of skillful means to serve as a broad and flexible concept that can inspire many new ideas and directions for the field.