Drug efficacy has been improved using various methods that enhance targeting, decrease toxicity, and facilitate timely and sustained drug release. To achieve these properties, various drug loading and release platforms have been developed. Layer-by-layer (LbL) self-assembly is widely used to generate controlled and sustained drug release LbL multilayer films because it allows desired functions and structures to be obtained through a simple procedure. In this review article, we highlight controlled drug release from LbL self-assembling films with diverse release kinetics, particularly with regard to mechanisms of drug release.