Metalloproteinases (MPs) belong to the superfamily of zinc endopeptidases, which are called metzincins. Three families of MPs have been studied in healthy and diseased conditions in humans. The first study on MPs was published in 1962, and following that, several studies characterized their activity and their effect on health and disease. Several diseases have been related to MPs, such as cardiovascular disease, cancer, inflammatory diseases, gynecological disorders, and others. Moreover, tissue inhibitors of metalloproteinases (TIMPs) have been widely studied, and drugs and artificial molecules that could target MP activity have been evaluated. MPs are relevant to public health because of their role in several diseases and, most of all, their role as biomarkers that also impact the quality of life and the psychosocial dimension of affected patients. In this context, new pathways to precision health and precision medicine have been opened in the area of MPs. This review describes, from the initial studies, the complex dimensions of MPs and related issues centered on health and disease dimensions.