The measurement of mitochondrial biogenesis is important in the determination of aging and disease processes and the assessment of countermeasurements to them. We argue that the frequently used assessments of cell signaling, mitochondrial protein mRNA, mitochondrial protein expression or enzyme activity, and mitochondrial density are not measurements that can lead to conclusions about mitochondrial biogenesis. Instead, we propose that only measurements of mitochondrial synthesis are indicative of biogenesis. Clarification of this issue will hopefully result in further differentiation of the processes important for morphological and functional changes of mitochondria.