Mitochondrial retrograde signaling is a pathway of communication from mitochondria to the nucleus that influences many cellular and organismal activities under both normal and pathophysiological conditions. In yeast it is used as a sensor of mitochondrial dysfunction that initiates readjustments of carbohydrate and nitrogen metabolism. In both yeast and animal cells, retrograde signaling is linked to TOR signaling, but the precise connections are unclear. In mammalian cells, mitochondrial dysfunction sets off signaling cascades through altered Ca2+ dynamics, which activate factors such as NFkappaB, NFAT, and ATF. Retrograde signaling also induces invasive behavior in otherwise nontumorigenic cells implying a role in tumor progression.