Mitochondria are semiautonomous organelles that are a defining characteristic of almost all eukaryotic cells. They are vital for energy production, but increasing evidence shows that they play important roles in a wide range of cellular signaling and homeostasis. Our understanding of nuclear control of mitochondrial function has expanded over the past half century with the discovery of multiple transcription factors and cofactors governing mitochondrial biogenesis. More recently, nuclear changes in response to mitochondrial messaging have led to characterization of retrograde mitochondrial signaling, in which mitochondria have the ability to alter nuclear gene expression. Mitochondria are also integral to other components of stress response or quality control including ROS signaling, unfolded protein response, mitochondrial autophagy, and biogenesis. These avenues of mitochondrial signaling are discussed in this review.