Mitochondria are considered as power plants of the cell. However, even during the normal function of the mitochondria the incomplete reduction of oxygen results in formation of reactive oxygen species (ROS). Overproduction of ROS jeopardizes the structural and functional integrity of mitochondria. Calcium transients originating from the cytosol and endoplasmic reticulum regulate ATP production by changing respiratory substrate availability and citric acid cycle activity. Overdriving the mitochondria with Ca²⁺ however, results in mitochondrial impairment with a concomitant decrease of ATP formation and enhanced ROS production. The present work summarizes the work done in our laboratory on isolated mitochondria with the aim to clarify interactions between the members of the triangle. This review highlights the effects of Ca²⁺ from the stimulation of respiration and ATP production through the moderate and reversible mitochondrial damage and increased ROS production to the permeability pore opening which represent the final stage of Ca²⁺-mediated functional and structural injury. We also discuss the possible role of mitochondria in the ROS elimination and its inhibition by Ca²⁺.