Distinct from classical tumor angiogenesis, vasculogenic mimicry (VM) provides a blood supply for tumor cells independent of endothelial cells. VM has two distinct types, namely tubular type and patterned matrix type. VM is associated with high tumor grade, tumor progression, invasion, metastasis, and poor prognosis in patients with malignant tumors. Herein, we discuss the recent studies on the role of VM in tumor progression and the diverse mechanisms and signaling pathways that regulate VM in tumors. Furthermore, we also summarize the latest findings of non-coding RNAs, such as lncRNAs and miRNAs in VM formation. In addition, we review application of molecular imaging technologies in detection of VM in malignant tumors. Increasing evidence suggests that VM is significantly associated with poor overall survival in patients with malignant tumors and could be a potential therapeutic target.