Freeze-drying, also known as lyophilization, has become a pivotal technique in pharmaceutical microencapsulation due to its ability to preserve the structural and functional integrity of encapsulated bioactive compounds. This method offers a unique advantage for the stabilization of sensitive pharmaceutical ingredients, such as proteins, peptides, and small molecules, by removing water under low temperature and pressure conditions, thus extending the shelf life of the final product. Microencapsulation involves incorporating active pharmaceutical ingredients (APIs) within a protective carrier material, typically polymers such as gelatine, alginate, or poly-lactic-co-glycolic acid (PLGA). This process not only protects the encapsulated drug from degradation but also provides enhanced stability during storage and transportation. This is particularly beneficial for temperature-sensitive formulations, where traditional drying techniques, such as spray drying, may cause heat-induced denaturation or loss of activity. The ability to tailor the porosity and morphology of the microspheres is another significant benefit, impacting the release profile of the encapsulated drugs. Additionally, the low processing temperatures associated with freeze-drying help preserve the functionality of sensitive biopharmaceuticals, making this technique suitable for encapsulating a wide range of active ingredients, including vaccines, enzymes, and growth factors. This chapter discusses the use of freeze-drying in pharmaceutical microencapsulation, focusing on its methodology, and its impact on the stability and release behaviour of encapsulated drugs. Current applications and future trends of freeze-drying in drug delivery systems are also explored.