The Buddha expresses dependent origination in a general formula: "When this is, that is. From the arising of this comes the arising of that. When this isn't, that isn't. From the cessation of this comes the cessation of that." Nothing arises independently; everything arises in dependence on conditions. Applied to the arising of suffering, this yields the twelve-link chain: ignorance conditions volitional formations, which condition consciousness, which conditions name-and-form, the six sense bases, contact, feeling, craving, clinging, becoming, birth, and finally aging, death, and suffering. The chain shows exactly how suffering originates — and therefore exactly how it can be brought to cessation.
The Buddha presents dependent origination explicitly as the middle way between two philosophical extremes. Eternalism holds that things have a permanent, unchanging essence that persists through time. Nihilism holds that things simply do not exist — that there is no continuity between past and present, no reality to persons or actions. Dependent origination avoids both: phenomena are real (not nothing) but arise and cease dependent on conditions (not permanent). This allows for continuity without essence — a person can be morally responsible for past actions without having an unchanging self that did them.
The chain begins with ignorance (avijja) — not ignorance of facts but the fundamental misperception of the nature of experience: taking impermanent things as permanent, taking not-self as self, taking suffering as satisfactory. This root ignorance conditions the volitional formations (sankhara) that shape consciousness and set the whole chain in motion. This is why the Buddhist path begins with Right View: if the root of the problem is cognitive — a misperception — then the beginning of the solution is cognitive. Not purely cognitive — the path requires training of body, speech, and mind — but requiring a fundamental reorientation of how things are seen.
Nagarjuna, the great Madhyamaka philosopher, extended dependent origination from a causal theory into a comprehensive metaphysics: all phenomena are empty (sunya) of inherent existence precisely because all phenomena arise in dependence on conditions. Nothing has a nature that is its own, independently of everything else. This doctrine of sunyata (emptiness) does not mean that things are nothing; it means that their being is entirely relational. The table is a table only in relation to the conditions — materials, carpentry, human purposes — that make it a table. Remove those conditions and the "table" dissolves into something else.
The twelve-link chain of dependent origination is primarily presented in the Samyutta Nikaya but is referred to throughout the Pali Canon. Its interpretation is contested: some scholars read it as a description of the causal process across multiple lifetimes; others read it as a description of the moment-to-moment arising of suffering within a single experience. The two readings are not mutually exclusive, and both are represented in the commentarial tradition.