Most solid cancer-related deaths result from metastasis, a multistep process in which cancer cells exit the primary site, intravasate into the bloodstream, extravasate, and colonize distant organs. Colonization is facilitated by clonal selection and the high phenotypic plasticity of cancer cells that creates reversible switching of cellular states. Cancer cell plasticity leads to intratumor heterogeneity and fitness, yielding cells with molecular and cellular programs that facilitate survival and colonization. While cancer cell plasticity is sometimes limited to the process of epithelial-to-mesenchymal transition (EMT), recent studies have broadened its definition. Plasticity arises from both cell-intrinsic and cell-extrinsic factors and is a major obstacle to efficacious anti-cancer therapies. Here, we discuss the multifaceted notion of cancer cell plasticity associated with metastatic colonization.