Macrophages are prevalent in the body and have roles in almost every aspect of human biology. They have often been considered a subject to avoid during drug delivery. However, with recent understanding of their diverse functions in diseases, macrophages have gained increasing interest as important therapeutic targets. To develop drug carriers to macrophages, it is important to understand their biological roles and requirements for efficient targeting. This review provides an overview of representative carriers and various approaches to address challenges in drug delivery to macrophages such as biodistribution, cellular uptake, intracellular trafficking, and drug release.