Influenza A virus (IAV) matrix protein 2 (M2) is among the smallest bona fide, hence extensively studied, ion channel proteins. The M2 ion channel activity is not only essential for virus replication, but also involved in modulation of cellular homeostasis in a variety of ways. It is also the target for ion channel inhibitors, i.e., anti-influenza drugs. Thus far, several studies have been conducted to elucidate its biophysical characteristics, structure-function relationships of the ion channel, and the M2-host interactome. In this review, we discuss M2 protein synthesis and assembly into an ion channel, its roles in IAV replication, and the pathophysiological impact on the host cell.