The Universe as we know it is condemned to death. Space, matter and even time will one day cease to exist and there's nothing we can do about it. Harsh realities are revealed about the future of our Universe; it may collapse and burn or it might be gripped by a galactic ice age. Either of these scenarios might be a long way off. However, our Universe could suddenly be destroyed by a "random quantum fluctuation", a bubble of destruction that can obliterate the entire cosmos in the blink of an eye. No matter how it ends, life in our Universe is doomed.

As man moves to colonize the cosmos, the realities of sexual relationships and reproduction need to be addressed. Probe the physiological, psychological and cultural challenges of sex in space.

When mankind eventually leaves the cradle of Earth and ventures forth into the uncharted territories of the cosmos, where, and what form, will our new homes take?

The story begins with Tyson sitting at a campfire, and telling how the wolf changed through artificial selection, and selective breeding into the dog breeds around today. He then enters the Ship of Imagination, and explains natural selection with the process that helped to create the polar bears. Along the way he talks about DNA, genes and mutation. Next he goes to a forest and describes the Tree of life, this leads him to discussing the evolution of the eye. He then discusses extinction, by going to a monument called the Halls of Extinction, dedicated to the broken branches of the tree of life. Explaining the five great Extinction events. He then tells how some life has survived, and then focuses on the tardigrade. From there he talks about what other kinds of life might have been created on other worlds. He then goes to Saturn's moon Titan. From there he speculates about life and how it first began. He then returns to Earth and tells about abiogenesis and how life changed and evolved. The show ends with an animated sequence from the original series of life's evolution from one cell to humans.

The episode begins with Tyson describing how pattern recognition manifested in early civilization as using astronomy and astrology to predict the passing of the seasons, including how the passage of a comet was often taken as an omen. Tyson continues to explain that the origin of comets only became known in the 20th century due to the work of Jan Oort and his hypothesis of the Oort cloud. Tyson then continues to relate the collaboration between Edmond Halley and Isaac Newton in the last part of the 17th century in Cambridge. The collaboration would result in the publication of Philosophiæ Naturalis Principia Mathematica, the first major work to describe the laws of physics in mathematical terms, despite objections and claims of plagiarism from Robert Hooke and financial difficulties of the Royal Society of London. Tyson explains how this work challenged the prevailing notion that God had planned out the heavens, but would end up influencing many factors of modern life, including space flight. Tyson further describes Halley's contributions including determining Earth's distance to the sun, the motion of stars and predicting the orbit of then-unnamed Halley's Comet using Newton's laws. Tyson contrasts these scientific approaches to understanding the galaxy compared to what earlier civilizations had done, and considers this advancement as mankind's first steps into exploring the universe. The episode ends with an animation of the Milky Way and Andromeda galaxies' merging based on the principles of Newton's laws.

Tyson begins the episode by explaining the nature of the speed of light and how much of what is seen of the observable universe is from light emanated from billions of years in the past. Tyson further explains how modern astronomy has used such analyzes via deep time to identify the Big Bang event and the age of the universe. Tyson proceeds to describe how the work of Isaac Newton, William Herschel, and James Clerk Maxwell contributed to understanding the nature of electromagnetic waves and gravitational force, and how this work led towards Albert Einstein's Theory of Relativity, that the speed of light is a fundamental constant of the universe and gravity can be seen as distortion of the fabric of space-time. Tyson describes the concept of dark stars as postulated by John Michell which are not visible but detectable by tracking other stars trapped within their gravity wells, an idea Herschel used to discover binary stars. Tyson then describes the nature of black holes, their enormous gravitational forces that can even capture light, and their discovery via X-ray sources such as Cygnus X-1. Tyson uses the Ship of Imagination to provide a postulate of the warping of spacetime and time dilation as one enters the event horizon of the black hole, and the possibility that these may lead to other points within our universe or others, or even time travel. Tyson ends on noting that Herschel's son, John would be inspired by his father to continue to document the known stars as well as contributions towards photography that play on the same nature of deep time used by astronomers.