In recent times, the requirement of more than one drug to cure a diseased condition is on the rise, and the delivery of these therapeutic substances to diseased locations with least toxicity is of immense significance in many recent pharmacological treatments. Over the years, we have witnessed advances in drug delivery, from devices that enable the introduction of a therapeutic substance into the body with the least toxicity to the body. These devices are able to deliver multiple therapeutic substances to specific organ(s) or diseased location(s) at a controlled rate with reduced toxic effects to the body. Hydrogel biocomposites have unique network structures that enable very high levels of hydrophilicity and biocompatibility, providing the ability to bio-mimic living tissue, making them ideal biomaterials. Several researchers have presented stimulus-responsive hydrogels, allowing for exceptional levels of control over polymer biomaterial properties in response to external signal(s). They can be designed to specifically target diseased location(s) by altering the method of delivery to specific required pharmacokinetics resulting in improved efficacy of pharmacological treatments. They have been reported to enhance groundbreaking advances in healthcare and allowing for more effective management of a countless diseases. The focus on the fundamentals of drug delivery systems, utilization of hydrogels for the sole purpose of drug delivery, multiple drug delivery and their applications in recent times will be covered in this chapter.