"[1] Frederic I. Carpenter wrote in the English Journal that the novel "essentially [...] described the struggle of all these lonely people to come to terms with their world, to become members of their society, to find human love—in short, to become mature.

The book begins with a focus on the relationship between two close friends, John Singer and Spiros Antonapoulos, deaf people who have lived together for several years.

The remainder of the narrative centers on the struggles of four of John Singer's acquaintances: Mick Kelly, a tomboy who loves music and dreams of buying a piano; Jake Blount, an alcoholic labor agitator; Biff Brannon, the observant owner of a diner; and Dr. Benedict Mady Copeland, an idealistic physician.

[19] When published in 1940, the novel created a literary sensation and enjoyed a rapid rise to the top of the bestseller lists; it was the first in a string of works by McCullers that give voice to those who are rejected, forgotten, mistreated or oppressed.

[3] Alice Hamilton wrote in the Dalhousie Review that the presence of so many mutes in the storyline "Taken literally [...] strains the bounds of credulity.

[22][23][24] British artist Joe Simpson made McCullers's book the centerpiece of his 2014 painting, The Heart Is A Lonely Hunter.