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Nearly half a million years ago, the most advanced human yet roams Europe. Strong and powerful, Homo heidelbergensis are fierce hunters, use sophisticated tools and live in close-knit family groups. Over 200,000 years they become split into two populations by extremes of weather and environment and evolve separately into two very different species. In the North are the Neanderthals, whose physical power and resilience is the key to surviving in ice age Northern Europe. About 140,000 years ago, Africa is in the grip of a devastating drought, and something remarkable has happened to the descendants of heidelbergensis who live there. The combination of environment and chance has bred in them a unique ability that will change the course of human history. It will be this small band of southern survivors, perhaps numbering just a few tens of thousands, who will come to dominate the world and be known as Homo sapiens.

xamines the fate of the Neanderthals, our European cousins who died out as modern humans spread from Africa into Europe during the Ice Age. Did modern humans interbreed with Neanderthals or exterminate them? The program explores crucial evidence from the recent decoding of the Neanderthal genome. How did modern humans take over the world? New evidence suggests that they left Africa and colonized the rest of the globe far earlier, and for different reasons, than previously thought. As for Homo sapiens, we have planet Earth to ourselves today, but that's a very recent and unusual situation. For millions of years, many kinds of hominids co-existed. At one time Homo sapiens shared the planet with Neanderthals, Homo erectus, and the mysterious "Hobbits"–three-foot-high humans who thrived on the Indonesian island of Flores until as recently as 12,000 years ago. "Last Human Standing" examines why "we" survived while those other ancestral cousins died out. And it explores the provocative question: In what ways are we still evolving today?

The simple act of making an apple pie is extrapolated into the atoms and subatomic particles (electrons, protons, and neutrons) necessary. Many of the ingredients necessary are formed of chemical elements formed in the life and deaths of stars (such as our own Sun), resulting in massive red giants and supernovae or collapsing into white dwarfs, neutron stars, pulsars, and even black holes. These produce all sorts of phenomena, such as radioactivity, cosmic rays, and even the curving of spacetime by gravity. Cosmos Update mentions the supernova SN 1987A and neutrino astronomy.

The idea of intelligence is explored in the concepts of computers (using bits as their basic units of information), whales (in their songs and their disruptions by human activities), DNA, the human brain (the evolution of the brain stem, frontal lobes, neurons, cerebral hemispheres, and corpus callosum under the Triune Brain Model), and man-made structures for collective intelligence (cities, libraries, books, computers, and satellites). The episode ends with speculation on alien intelligence and the information conveyed on the Voyager Golden Record.

This episodes the nature of the cosmos on the micro and atomic scales, using the Ship of the Imagination to explore these realms. Tyson describes some of the micro-organism that live within a dew drop, demonstrating parameciums and tardigrades. He proceeds to discuss how plants use photosynthesis via their chloroplasts to convert sunlight into chemical reactions that convert carbon dioxide and water into oxygen and energy-rich sugars. Tyson then discusses the nature of molecules and atoms and how they relate to the evolution of species. He uses the example set forth by Charles Darwin postulating the existence of the long-tongued Morgan's sphinx moth based on the nature of the comet orchid with pollen far within the flower. He further demonstrates that scents from flowers are used to trigger olfactory centers in the brain, stimulating the mind to threats as to aid in the survival of the species. Tyson narrates how Greek philosophers Thales and Democritus postulated that all matter was made up of combinations of atoms in a large number of configurations, and describes how carbon forms the basic building block for life on earth due to its unique chemical nature. Tyson explains on the basic atomic structure of protons, neutrons, and electrons, and the nature of nuclear fusion that occurs in most stars. He then discusses the existence of neutrinos that are created by these nuclear processes in stars, and that detecting such sub-atomic particles which normally pass through matter require subterranean facilities like the Super-Kamiokande that were used to detect neutrinos from the supernova SN 1987A in the Large Magellanic Cloud before light from the explosion were observed due to their ability to pass through matter of the dying sun. Tyson compares how neutrinos were postulated by Wolfgang Pauli to account for the conservation of energy from nuclear reactions in the same manner as Darwin's postulate on the long-tongued moth. Tyson concludes by noting that there are neutrinos from the Big Bang still existing in the universe but due to the nature of light, there is a "wall of infinity" that cannot be observed beyond.

In the fourth episode of the series, Clovis was the first Frankish king to acknowledge the Christian faith. This changed the direction of Europe's history.