The incurability of metastatic cancer is currently an unmet clinical need which needs to be addressed. This Special Issue on Metastasis highlights the ongoing challenges in the field and research being undertaken to more thoroughly understand models of metastasis, disrupt the metastatic cascade, and improve treatment outcomes for patients. Curated by Suzanne Fuqua (Baylor College of Medicine, USA), the Special Issue contains a selection of articles and commissioned content from leading researchers, to present a broad-scope view of current research focal points and explore future directions of cancer metastasis.