More than 60 years ago Aristides Leão coined the term spreading depression (SD) to describe a transient “depression” of electrocorticographic activity that lasts up to several minutes and slowly “spreads” in all directions in cortex by way of gray matter contiguity.1 Today we know that SD is an intrinsic electrophysiological property of central nervous systems, evolutionarily preserved from locust to man.2-7 Largely based on the similarities between the symptomatology of migraine aura and the electrophysiological features of SD, a causal relationship between the two has long been hypothesized.8-10 Recently, the SD theory of migraine gained momentum by evidence emerging from both clinical and experimental studies despite being challenged by alternative mechanisms and hypotheses. Here, I will review the accumulated evidence supporting a causal relationship between SD and migraine aura and headache, and discuss the contested notion that SD may also be involved in migraine attacks without a “perceived” aura.