Macrophages are critical effector cells of the innate immune system. The presence of microbes or the stimulation by inflammatory factors triggers the metabolic reprogramming of macrophages or macrophage polarization into two phenotypes: the classically activated macrophages (M1) displaying a pro-inflammatory phenotype and the alternatively activated macrophages (M2) having anti-inflammatory functions. The imbalance between the two phenotypes has been linked with various pathological states, such as fibrosis, hepatitis, colitis, and tumor progression. An avenue of potential therapeutic strategies based on macrophage polarization has emerged. Therefore, it is essential to understand the mechanisms of macrophage polarization. In this review, we focus on the macrophage polarization process and discuss the stimuli-dependent conversion into M1 and M2 phenotypes. We also present the metabolic patterns supporting their specific functions. The factors and signaling cascades involved in intra-class switching are also detailed. Finally, the role of macrophage polarization in disease progression is discussed.