The cardiac glycoside ouabain, a well-known inhibitor of the Na/K ATPase pump, is also known to activate different cell signaling pathways that are unrelated to pump inhibition. Ouabain has, for many years, been used for congestive heart failure, but it has been suggested that its effects can be extended to other diseases. Drug repositioning of substances already in use for other indications is less time and cost consuming. The present work reviews what is known about ouabain and cancer. A wide concentration range, from pM to mM, has been studied in various experimental models. These models considered ouabain’s direct action on tumor cells, effects on the inflammatory and immune responses, as well as the tumor microenvironment.