Sagan discusses the story of the Heike crab and artificial selection of crabs resembling samurai warriors, as an opening into a larger discussion of evolution through natural selection (and the pitfalls of intelligent design). Among the topics are the development of life on the Cosmic Calendar and the Cambrian explosion; the function of DNA in growth; genetic replication, repairs, and mutation; the common biochemistry of terrestrial organisms; the creation of the molecules of life in the Miller-Urey experiment; and speculation on alien life (such as life in Jupiter's clouds). In the Cosmos Update ten years later, Sagan remarks on RNA also controlling chemical reactions and reproducing itself and the different roles of comets (potentially carrying organic molecules or causing the Cretaceous–Paleogene extinction event).

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.

Questions are raised about the search for intelligent life beyond the Earth, with UFOs and other close encounters refuted in favor of communications through SETI and radio telescope such as the Arecibo Observatory. The probability of technically advanced civilizations existing elsewhere in the Milky Way is interpreted using the Drake equation and a future hypothetical Encyclopedia Galactica is discussed as a repository of information about other worlds in the galaxy. The Cosmos Update notes that there have been fewer sightings of UFOs and more stories of abductions, while mentioning the META scanning the skies for signals.

Sagan reflects on the future of humanity and the question of 'who speaks for Earth?' when meeting extraterrestrials. He discusses the very different meetings of the Tlingit people and explorer Jean-François de La Perouse with the destruction of the Aztecs by Spanish conquistadors, the looming threat of nuclear warfare, and the threats shown by destruction of the Library of Alexandria and the murder of Hypatia. The episode ends with an overview of the beginning of the universe, the evolution of life, and the accomplishments of humanity and makes a plea to mankind to cherish life and continue its journey in the cosmos. The Cosmos Update notes the preliminary reconnaissance of planets with spacecraft, the fall of the Berlin Wall and the end of apartheid in South Africa, and measures towards the reduction of nuclear weapons.

The word Anunnaki means "princely seed" or "princely blood". The idea is that the Anunnaki were direct creations of Anu, who was regarded as the father and king of the gods. Ancient Aliens: "In the ancient texts of Sumeria we have descriptions of these being descending from the sky called the Anunnaki. The term Anunnaki means 'those who from the heavens came."

The Nazca Lines of Peru have been an important part of the Ancient Astronaut theory since its beginning. Originally Von Daniken claimed that the lines were kind of a UFO runway, or a type of alien airport, where the alien craft landed and took off. The idea that it was an airport makes no logical sense, and the symbols and rituals which were a huge part of the Nazcan culture more than explain the so called Nazca lines.