Throughout the animal kingdom, mitochondria are the only organelles that retain their own genome and the transcription and translation machineries that are all essential for energy harvesting. Mitochondria have developed a complex communication network, allowing them to stay in tune with cellular needs and nuclear transcriptional programs and to alleviate mitochondrial dysfunction. Here, we review recent findings on the wide array of mechanisms that contribute to these mitocellular communication networks, spanning from well-studied messenger molecules to mitonuclear genetic interactions. Based on these observations and developments, we advocate a broad and inclusive view on mitocellular interactions, which can have profound impacts on physiological, pathological, and evolutionary processes.