Doctor Zhivago was finally published in the Soviet Union in 1988, in the pages of Novy mir, although earlier samizdat editions existed.

Yuri Zhivago is sensitive and poetic nearly to the point of mysticism. In medical school, one of his professors reminds him that bacteria may be beautiful under the microscope, but they do ugly things to people.

Zhivago's idealism and principles stand in contrast to the brutality and horror of World War I, the Russian Revolution, and the subsequent Russian Civil War. A major theme of the novel is how mysticism and idealism are destroyed by both the Bolsheviks and the White Army alike, as both sides commit horrible atrocities. Yuri witnesses dismemberment and other horrors suffered by the innocent civilian population during the turmoil. Even the love of his life, Lara, is taken from him.

He ponders on how war can turn the whole world senseless, and make an otherwise reasonable group of people destroy each other with no regard for life. His journey through Russia has an epic, dreamlike, almost surreal feeling because of his traveling through a world which is in such striking contrast to himself, relatively uncorrupted by the violence, and to his desire to find a place away from it all, which drives him across the Arctic Siberia of Russia, and eventually back to Moscow. Pasternak gives subtle criticism of Soviet ideology: he disagrees with the idea of "building a new man," which, he suggests, is against nature.

Lara's life is also dealt with in considerable detail. Lara, whose full name is Larissa Feodorovna Guishar (later Antipova), is the daughter of a bourgeois mother. She becomes involved in an affair with Viktor Komarovsky, a powerful lawyer with political connections, who both repulses and attracts her. Lara is engaged to Pavel "Pasha" Antipov, an idealistic young student who becomes involved in Bolshevism through his father. To gain independence from Komarovsky, Lara spends three years working as a live-in nanny for a wealthy family (the Kologrivovs). Upon returning her brother begs her to get 700 rubles from Komarovsky to repay money that he has gambled away. Lara gets the money for her brother from her generous employer, Kologrivov. However, when her pupil Lipa graduates, she feels like she is on charity instead of working for her keep in the Kologrivov household. She decides that Komarovsky "owes her" and she will get money from him with which she will become independent. She goes to a party to demand the money from Komarovsky. He is playing cards all evening and she does not get his attention. She finally walks in and attempts to shoot him but misses.

Zhivago briefly encounters Lara while assisting his mentor who has been called by Komarovsky to the scene of the attempted suicide of Lara's mother in response to Lara's and Komarovsky's scandalous relationship. Zhivago also sees Lara at the Christmas party where she tries to shoot Komarovsky. Lara and Zhivago truly meet following a roadside encounter between First World War troop columns, one group being miserable retreating Russian Army deserting veterans and the other group are new recruits bound for the hopeless conditions at the Front. Lara has been serving as nurse while searching for her assumed-dead husband Antipov. The two fall in love as they serve together in a makeshift field hospital. They do not consummate their relationship until much later, meeting in the town of Yuriatin after the war.

Pasha Antipov and Komarovsky continue to play important roles in the story. Pasha is assumed killed in World War I, but is actually captured by the Germans and escapes. Pasha Antipov joins the Bolsheviks and becomes Strelnikov (the shooter), a fearsome Red Army general who becomes infamous for executing White prisoners (hence his nickname). However, he is never a true Bolshevik and yearns for the fighting to be over so he can return to Lara. (The film version would change his character significantly, making him a hard-line Bolshevik.)

Another major character is Liberius, commander of the "Forest Brotherhood", the Red Partisan band which conscripts Yuri into service. Liberius is depicted as loud-mouthed and vain, a dedicated and heroic revolutionary, who bores Yuri with his continuous lectures on the justice of their cause and the inevitability of their victory. He is also addicted to cocaine.

Komarovsky reappears towards the end of the story. He has gained some influence in the Bolshevik government and been appointed minister of justice of the Far Eastern Republic, a Bolshevik puppet state in Siberia. He offers Zhivago and Lara transit out of Russia. They initially refuse, but by lying about Pasha Antipov's death Komarovsky privately persuades Zhivago that it is in Lara's best interests to leave; Zhivago convinces Lara to go with Komarovsky, telling her (falsely) that he will follow her shortly.

Meanwhile, Antipov/Strelnikov falls from grace, loses his position in the Red Army, and returns to Varykino, near Yuriatin, where he hopes to find Lara. She, however, has just left with Komarovsky. After having a lengthy conversation with Zhivago, Pasha Antipov commits suicide and is found the next morning by Zhivago. (In the movie Komarovsky tells Zhivago that he was captured 5 miles outside of Yuriatin and on the way to his execution he grabbed a pistol from a guard and killed himself.) Zhivago's life and health go downhill from this point; he lives with another woman and has two children with her, plans numerous writing projects but does not finish them, and is increasingly absent-minded, erratic, and unwell. Lara eventually returns to Russia on the day of Zhivago's funeral. She gets Yevgraf, his half brother, to try to find her daughter but then disappears.