Tenderness depends on multiple factors, intervening throughout the production chain, from animal's birth till the end of meat aging. Given the striking number of variables, it is not an exaggeration to affirm that meat coming from each individual is a ‘unique’ meat. So, the process of meat tenderization follows different paths; meat derived from different animals shows its own evolution, but underneath the wide variability, all these individual developments follow a standard template: in other words, there are some boundaries that limit the possible variations. This review wants to give a comprehensive idea of the concept of meat tenderness, in particular focusing on the two protein classes that are among the most important direct responsibles for tenderization: sarcomeric proteins and proteolytic enzymes. We will review the most recent and significant data acquired on each protein, pointing the attention on the results collected by means of the ‘omics’ technologies, and underlining the possible role of markers in the frame of meat tenderness.