Migraine is among the most common and most disabling disorders worldwide, yet its underlying pathophysiology is among the most poorly understood. New information continues to emerge on mechanisms within the central and peripheral nervous systems that may contribute to migraine attacks. Additionally, new therapeutics have recently become available and along with much needed relief for many patients, these drugs provide insight into the disorder based on their mechanism of action. This review will cover new findings within the last several years that add to the understanding of migraine pathophysiology, including those related to the vasculature, calcitonin gene-related peptide (CGRP), and mechanisms within the cortex and meninges that may contribute to attacks. Discussion will also cover recent findings on novel therapeutic targets, several of which continue to show promise in new preclinical studies, including acid-sensing ion channels (ASICs) and the delta-opioid receptor (DOR).