The story is told by a series of progress reports written by Charlie Gordon, the first human subject for the surgery, and it touches on ethical and moral themes such as the treatment of the mentally disabled.

[4] Although the book[5] has often been challenged for removal from libraries in the United States and Canada, sometimes successfully, it is frequently taught in schools around the world and has been adapted many times for television, theater, radio and as the Academy Award-winning film Charly.

[11] He therefore made his story's main character a person who was initially "lowborn" (a mentally disabled young man) who then became a "highborn" after the intelligence-enhancing procedures.

[13][better source needed] Nemur and Strauss, the scientists who develop the intelligence-enhancing surgery in the story, were based on professors Keyes met while in graduate school.

[11] In 1958, Keyes was approached by Galaxy Science Fiction magazine to write a story, at which point the elements of Flowers for Algernon fell into place.

[13][better source needed] When the story was submitted to Galaxy, however, editor Horace Gold suggested changing the ending so that Charlie retained his intelligence, married Alice Kinnian, and lived happily ever after.

[18] The Magazine of Fantasy & Science Fiction reprinted the original short story in its May 2000 issue along with an essay titled "Algernon, Charlie and I: A Writer's Journey" by the author.

[22][better source needed] [23] The short story and the novel share many similar plot points, but the novel expands significantly on Charlie's developing emotional state as well as his intelligence, his memories of childhood, and the relationship with his family.

The mouse loses his increased intelligence and mental age and dies afterward; Charlie buries him in the back yard of his home.

He resumes his old job as a janitor at the factory and tries to go back to how things used to be, but he cannot stand the pity and guilt from those around him, including his co-workers, his landlady, and Ms. Kinnian.

Desiring to improve himself, Charlie attends reading and writing classes, taught by Miss Alice Kinnian, at the Beekman College Center for Retarded Adults.

Two researchers at Beekman, Professor Nemur and Dr. Strauss, are looking for a human test subject on whom to try a new surgical technique intended to increase intelligence.

Based on Alice's recommendation and his motivation to improve, Nemur and Strauss choose Charlie over smarter pupils to undergo the procedure.

At the same time, he begins recalling his childhood and remembers that his mother Rose physically abused him and wasted money on fake treatments for his disability, while his younger sister Norma resented him.

In his research, he discovers a flaw behind Nemur and Strauss's procedure that indicates he might lose his intelligence and possibly regress back to his previous state.

Unable to bear the thought of being dependent and pitied by his friends and co-workers, he decides to live at the Warren State Home and Training School, where no one knows about the operation.

Both the novel and the short story are written in an epistolary style collecting together Charlie's personal "progress reports" from a few days before the operation until he regresses back to his original state almost five months later.

"[11] As an imbecile, Charlie is initially an unreliable narrator who presents the story through an immature worldview; his low intelligence compromises his ability to understand the world around him.

Important themes in Flowers for Algernon include the treatment of the mentally disabled,[4][26] the impact on happiness of the conflict between intellect and emotion,[27][28] and how events in the past can influence a person later in life.

The short story version of Flowers for Algernon was voted third out of 132 nominees and was published in The Science Fiction Hall of Fame, Volume One, 1929–1964 in 1970.

[33] Keyes was elected the SFWA Author Emeritus in 2000 for making a significant contribution to science fiction and fantasy, primarily as a result of Flowers for Algernon.

[35][better source needed] Many of the challenges have proved unsuccessful, but the book has occasionally been removed from school libraries, including some in Pennsylvania and Texas.

[36][better source needed] Flowers for Algernon has been the inspiration for works that include the album A Curious Feeling by Genesis keyboardist Tony Banks.

[40] Algernon is referenced in a 2013 episode of the TV series Brooklyn Nine-Nine titled "The Tagger" as the name of a mouse living in Detective Jake Peralta's desk.