The realization that hyperthermia was an ideal complementary treatment to radiation and certain chemotherapeutic agents from a biologic perspective led to great enthusiasm for this modality over a quarter of a century ago. Unfortunately, this well-deserved enthusiasm quickly become tempered because of the inability to effectively heat tumors, particularly deep-seated ones with cumbersome first generation technology coupled with still-emerging understandings of thermal biology. Today as before, both challenges and opportunities remain in the application of hyperthermia for cancer patients. The lessons learned from the introduction of hyperthermia, a generation ago, are providing focus for application of this still-promising modality in today's clinic. These areas of challenge and opportunity include: thermal biology; treatment planning, delivery, and monitoring; successful high-quality clinical trials; and integration of thermal therapy with emerging technologies and therapeutic strategies both established and evolving. The progress made in understanding of thermal biology, physics, and bioengineering, coupled with advances in complementary clinical treatment modalities have all contributed to the next generation of clinical thermal therapy.