Cancer has become one of the most difficult health challenges of our time, accounting for millions of deaths yearly. Systemic chemotherapy is the most common therapeutic approach; however, considerable limitations exist including toxicities to healthy tissues and low achievable drug concentrations at tumor sites. More than 85% of human cancers are solid tumors, which can greatly benefit from localized delivery. This approach allows for high drug concentrations at the target site, lower systemic toxicity, and extended drug exposure which may be beneficial for cell cycle-specific drugs. Polymers have been widely considered in the development of localized delivery systems. This review focuses on both natural and synthetic biodegradable polymers that have been explored for localized chemotherapy, exploring their advantages, disadvantages, and clinical potential while citing examples of their use in pre-clinical development.