A number of distinct endogenous and exogenous factors have been implicated in migraine precipitation but the exact nature of the triggering process itself and its relationship to the genesis of the headache remains largely speculative. In this article, we examine the potential sites and downstream cascades through which migraine triggers might exert their action to promote the activation of the migraine pain pathway. We further look at the laterality of the headache as a potential indicator for the site of migraine pain initiation and examine the question of triggering factor specificity in relation to the current understanding of migraine pathophysiology.