The opioid crisis remains a significant public health challenge, with opioid misuse, dependence, and mental health comorbidities posing serious concerns for patients and healthcare providers alike. Extended-release (ER) formulations of opioids have been developed as a means to provide stable analgesia while mitigating risks associated with immediate-release (IR) formulations. This paper critically examines how ER formulations of safer opioids can enhance medication adherence, reduce withdrawal symptoms, minimize abuse potential, and lower the mental health burdens associated with opioid use and misuse. The analysis is based exclusively on research findings published, ensuring a historical perspective on the evolution of ER opioid formulations and their clinical implications.