Having described and explored the global to individual context of climate change and health, this chapter now explores the biological imperative of any organism to maintain homeostasis. As a key function of this imperative, in humans, the cardiovascular system plays a key role in maintaining homeostasis. Over time we (humans) have overcome many of the biological limitations/constraints of these protective mechanisms through a combination of behavioural, cultural and technological adaptations—thereby allowing us to migrate and thrive in nearly every corner of the world. Within this biological to historical context, rapid climate change (through exposure to more weather extremes) is now challenging the limits of our ability to maintain homeostasis. How the opposing forces of human adaptability, maintaining thermoregulation and increasing climatic provocations to health plays out in vulnerable individuals and communities (from those living in poverty to older individuals living with chronic heart disease) will provide important context to later chapters.