Out of whack, unsatisfactory, unpleasant, suffering.
Dukkha is one of the Three Foundations of Existence, sometimes referred to as the Three Characteristics of Existence. Wisdom arises when a meditator realizes all three of the Three Foundations of Existence. The other two are anatta and annica.
However, one can see the Three Foundations without seeing dependent origination. Wisdom is thus short of Buddhahood.
The First Noble Truth is: Life is dukkha. The unenlightened believe that every member of the human dharma realm is on death row, that life always ends.
I saw a chalk-written and thus quite temporary sign on a sidewalk in front of a coffee shop in Brooklyn (The Cup, in Greenpoint) in March 2012. It said: “Life is a sexually transmitted fatal disease.” A funny comment, as intended.
The Buddha taught otherwise. The self has no ending because it has no beginning. It is suffering that begins and suffering that ends, and there is no sufferer.
The Diamond Sutra makes this point quite well.