The General in His Labyrinth is a fictionalized version of the last seven months of the life of the Colombian Grande leader Simón Bolívar, or "the General," as he is mostly referred to in the book. At that time, Bolívar had just resigned his presidency and, under threat of assassination, was making his way through South America to Europe. As such, many of the most important quotes in this book concentrate on dismantling Bolívar's legend and legacy and looking at him from the viewpoint of a vulnerable human being.

In the novel, he is suffering from tuberculosis, and his once impressive physical and mental capabilities have severely deteriorated. The characters are even concerned whether he will make it through the next few months.

The General discovered he was losing height as well as weight . . . his body was pale and his face and hands seemed scorched by exposure to the weather. He had turned forty-six this past July, but his rough Caribbean curls were already ashen, his bones were twisted by premature old age, and he had deteriorated so much he did not seem capable of lasting until the following July.

He is a far cry from the young man who had liberated Columbia Grande.

He had fought all his wars in the front lines, without suffering a scratch, and he had moved through enemy fire with such thoughtless serenity that even his officers accepted the easy explanation that he believed himself invulnerable. He had emerged unharmed from every assassination plot against him.

Just how much the General has deteriorated is highlighted by the descriptions of some of the other officers in the book— for example, that of Carlos Santos:

Casildo Santos, a former captain in the battalion of the Marksmen of the Guard who had a voice like thunder, a pirate's patch over his left eye, and a somewhat undaunted notion of his authority.

and that of General O'Leary:

At the opposite extreme was General O'Leary, who was tall and blond and had an elegant appearance enhanced by his Florentine uniforms. He had come to Venezuela at the age of eighteen as a second lieutenant in the Red Hussars and spent his entire career fighting in almost all the battles of the wars for independence.

Even his loyal servant seems more impressive than a man who no longer has the strength to grip a cup.

In the half-light the clear blue eyes, the curly squirrel-colored hair, the impassive dignity of the steward who attended him every day and who held in his hand a cup of the curative infusion of poppies and gum Arabic.

The General's servant José Palacios has been so long in service to the General that his loyalty seems more like a habit.

José Palacios had entered his service when he was very young, by order of the General's mother, who was his owner, and he had not been emancipated in a formal way. He was left floating in a civil limbo in which he was never paid a salary and his status was not defined, but his personal needs formed part of the private needs of the General, with whom he identified ever in his manner of dressing and eating and in his exaggerated sobriety.

The author suggests that when the General dies, so does José's spirit.

José Palacios remained in Cartagena de Indias at the mercy of public charity, attempted to drown his memories in alcohol, and succumbed to its pleasures. He died at the age of seventy-six in a den of beggars.