ROCK belongs to the AGC family of Ser/Thr protein kinases that are involved in many cellular processes. ROCK-driven actomyosin contractility regulates cytoskeletal dynamics underpinning cell migration, proliferation, and survival in many cancer types. ROCK1/2 play key protumorigenic roles in several subtypes and stages of cancer development. Therefore, successfully targeting ROCK and its downstream effectors presents an interesting avenue for cancer treatment. Because local use of ROCK inhibitors will reduce the side effects of systemic administration, we propose different therapeutic strategies and latest-generation ROCK inhibitors for use in the clinic.