On the surface, the title – One Hundred Years of Solitude – seems pretty clear. The novel is set in the fictional town of Macondo, a place that's totally isolated from the rest of Colombia by swamps, mountains, and jungles. Eventually technology reaches even this tiny place, but it takes a while: one hundred years, give or take a few.
But that's just the surface, and we here at Shmoop always come armed with shovels. Check out how García Márquez chooses the word "solitude" rather than "isolation" or "remoteness." They all kind of mean the same thing, but when you think "solitude" you think of one person, not a whole town. So the title can also be read as an armchair diagnosis of many of the members of the Buendía family, who all kind of exist together but are emotionally disconnected.
A little more digging and we can think about the timeframe of the title. Why a century? Well, it's a nice round number, and it highlights the huge transformation Colombia went through from the middle of the nineteenth century to the middle of the twentieth. Check out the "Setting" section for more on this.