The majority of cancer-related deaths can be attributed to the recurrence of the disease either in the same tissue or in a secondary tissue. Relapse of the disease is caused by dormant tumor cells, which have successfully resisted the therapeutic attack. Dormancy of the primary tumors and metastatic cells in distal tissues has become a point of importance for various reasons. The decision taken by a growing tumor to choose between a metabolically active state or a dormant state depends on various factors. This process is parallelly facilitated by the primary and secondary tumor microenvironment, which is comprised of cells and extracellular matrix (ECM). Acellular and cellular components of the extracellular matrix are known to influence the growth and progression of the tumor. Along with its pro-metastatic and pro-angiogenic signaling, ECM can also provide molecular and cellular cues to arrest tumor growth and maintain it in a quiescent state. Dormancy of primary tumors can be supported by the ECM, as of the disseminated tumor cells within the secondary tissue. Interestingly, the extracellular matrix can also play a critical role in the awakening of such dormant cells by activating different signal transduction pathways. The dual role of extracellular matrices in induction and abrogation of dormancy makes it a crucial target for therapeutics. This chapter is designed to discuss the components of extracellular matrix of primary and secondary tumors and their role in different aspects of tumor biology, specifically in dormancy.