Lysozyme is an enzyme existing in multiple organisms where it plays various vital roles. The most important role is its antibacterial activity in the human body; in fact, it is also called “the body's own antibiotic”. Despite its proven utility, lysozyme can potentially trigger allergic reactions in sensitive individuals, even in trace amounts. Therefore, lysozyme determination in foods is becoming of paramount importance. Traditional detection methods are expensive, time-consuming and they cannot be applied for fast in-situ quantification. Electrochemical and optical sensors have attracted an increasing attention due to their versatility and ability to reduce the disadvantages of traditional methods. Using an aptamer as the bioreceptor, the sensor selectivity is amplified due to the specific recognition of the analyte. This review is presenting the progresses made in lysozyme determination by means of electrochemical and optical aptasensors in the last five years. A critical overview on the methodologies employed for aptamer immobilization and on the strategies for signal amplification of the assays will be described. Different optical and electrochemical aptasensors will be discussed and compared in terms of analytical performances, versatility and real samples applications.