As the most abundant protein in mammals and a major structural component in extracellular matrix, collagen holds a pivotal role in tissue development and maintaining the homeostasis of our body. Persistent disruption to the balance between collagen production and degradation can cause a variety of diseases, some of which can be fatal. Collagen remodeling can lead to either an overproduction of collagen which can cause excessive collagen accumulation in organs, common to fibrosis, or uncontrolled degradation of collagen seen in degenerative diseases such as arthritis. Therefore, the ability to monitor the state of collagen is crucial for determining the presence and progression of numerous diseases. This review discusses the implications of collagen remodeling and its detection methods with specific focus on targeting native collagens as well as denatured collagens. It aims to help researchers understand the pathobiology of collagen-related diseases and create novel collagen targeting therapeutics and imaging modalities for biomedical applications.