This chapter examines codeine, a commonly used opioid analgesic that remains relevant in the treatment of mild to moderate chronic pain. It offers a comprehensive overview of codeine’s pharmacology, clinical indications, and its role within multimodal pain management approaches. As a prodrug primarily metabolized via the CYP2D6 enzyme into morphine, codeine’s analgesic efficacy and safety profile are heavily influenced by genetic polymorphisms, leading to significant interindividual variability. The chapter explores this metabolic variability and its implications for prescribing, especially in vulnerable populations such as pediatric, geriatric, and pregnant patients. Common side effects and clinical safety concerns are also addressed. The chapter concludes with guidance on appropriate patient selection and a balanced appraisal of codeine’s risks and benefits within a modern pain management framework.