Polymeric microspheres (MSs) and nanospheres (NSs) composed of synthetic and natural polymers can encapsulate anticancer drugs, among other therapeutics, acting as drug carriers to release them at controlled rates over long periods of time. These carriers present several potential advantages including simple preparation methods, suitable control over the sustained release of medications or stem cells, triggered release resulting from stimulus-responsive delivery, improved physical properties such as porosity and stable scaffolds for tissue engineering, and possible applications as microreactors and nanoreactors compared to conventional drug delivery systems. Moreover, many of these factors can impact drug release rates by polymeric MSs and NSs. Herein, drug delivery systems based on polymeric MSs and NSs are described and compared according to recent advances and challenges, and poignant thoughts on what the field needs to progress are presented.