Long-acting injectables (LAIs) have revolutionized the treatment of chronic diseases as they provide the patient with longer dosing intervals resulting in better adherence. In this chapter, we discuss the clinical use of biodegradable LAIs, which are capable of maintaining drug concentrations in the blood stream or within a given target site. Of interest, we describe the basis of the clinical implementation of LAIs and illustrate their usages for long-term management of chronic conditions, such as psychotic diseases, hormone disorders, cancers, allergic inflammations and diabetes. Moreover, recent advances towards clinical development of LAIs for local and systemic treatment of diverse chronic diseases are discussed.