According to “Amprino's rule”, the histological structure of primary bone tissue is directly dependent on the rate of subperiosteal accretion. This general statement is of considerable practical interest, especially for assessing growth rate and, hence, inferring the gross type of metabolic activity, in extinct taxa. Several experimental studies based on in vivo labeling of bone growth have been conducted in a comparative perspective to check the validity of Amprino's rule. Results confirmed its basic accuracy. They also revealed discrepancies among taxa for some types of tissues. The present chapter reviews the main data currently available on this topic and the questions remaining to be addressed.