Abstract: Metastasis is responsible for the greatest number of cancer deaths. Metastatic disease is closely related to the cell cytoskel-eton, but studies on various cytoskeletal components are relatively separated and scattered. At the same time, an emerging role for microtubules (MTs) in tumor cell metastasis is being unraveled by numerous research studies. The crosstalk between key MT interact-ing proteins and the actin cytoskeleton has received increased interest, which may result in novel treatment avenues for metastatic dis -eases. In this review, we will discuss the structure and function of the cell cytoskeleton, the key signaling pathways between cytoskele-tal-associated proteins, new related research, and anticancer drugs. In addition, we cite novel therapeutics and provide an overview of the mechanisms mediating the effects of the cytoskeleton and its interacting partners on tumor cell migration and metastasis.