ObjectivePlasminogen system plays a crucial role in physiological and pathological events related to tissue regeneration, wound healing, immune response, angiogenesis, invasion and metastasis. It gets activated when plasminogen associates with its cell surface receptors. Latest information on some of the well-explored plasminogen receptors such as annexin II-S100A10, cytokeratin 8, α-enolase, plasminogen receptor (KT) (Plg-R(KT)) and histone H2B has been discussed in the present review. These receptors can pave the way for effective new therapeutic and diagnostic strategies to counteract malignant diseases.ConclusionThe present review concludes the key role of plasminogen receptors in extracellular matrix degradation, infiltration into surrounding tissues, neovascularization, invasion, metastasis and drug resistance. This review also discusses the possible effect of blocking these plasminogen receptors with monoclonal antibodies and DNA-based vaccination or silencing plasminogen receptor gene using small interfering RNA or short hairpin RNA to counteract cancer invasion and metastasis.