Today, in the era of modern medicine, the sustained drug delivery is a major challenge, as conventional delivery approaches like oral, intravenous and transdermal have various shortcomings. Traditional delivery avenues affect the bioavailability, specific target location, immunogenicity, efficacy, cytotoxicity and safety of the drug, which leads to administration of multiple or high amounts of drug doses resulting in low to severe magnitudes of medical complications to the patients. Sustained drug delivery systems using the biopolymers as medium are promising materials as they can overcome the sudden release, enhancing efficacy and safety of drugs. One such polymer is cellulose, which is the most abundant polysaccharide and is procured from different sources like plants, wood, bacteria, algae and chordate animals such as tunicates. Cellulose and its derivatives have charmed the researchers, by several exclusive attributes such as functionality, high mechanical robustness and flexibility, high surface area, optical transparency, low density and biodegradability. The porosity and interconnectivity between cellulose-based polymeric formulations can be controlled for relevant biomedical applications. The commonly existing cellulosic derivatives are cellulose ethersCellulose Ethers (CE)and cellulose estersCellulose esters. Despite several unique features, cellulose has some limitations like low solubility, sensitivity to moisture and susceptibility to microbes, which pose challenges like optimal drug delivery, sustained release, hemocompatibility, immunogenicity, off-target toxicity and biodegradability. This chapter will address the overview of cellulose-based biomaterials, their modifications and characteristics and role in various promising therapeutics in the field of biomedicine.