Cellular organelles do not function as isolated or static units, they form dynamic contacts with each other that can be modulated according to cellular needs. The physical interfaces between organelles are important for Ca2+ and lipid homeostasis, and serve as a platform for many processes that include metabolic regulation, localized signaling mechanisms, organelle quality control and the apoptotic program. Emerging evidence also highlights the importance of organelle communication in disorders such as Alzheimer's disease, pulmonary arterial hypertension, cancer, skeletal and cardiac muscle dysfunction. Here, we overview the current literature on organelle communications and its link with human pathologies.