Local anesthetics are frequently employed during surgery in order to control peri-and postoperative pain. Retrospective studies have revealed an unexpected correlation between increased long-term survival and the use of local anesthetics during oncological surgery. This effect of local anesthetics might rely on direct cytotoxic effects on malignant cells or on indirect, immune-mediated effects. It is tempting to speculate, yet needs to be formally proven, that the combination of local anesthetics with oncological surgery and conventional anticancer therapy would offer an opportunity to control residual cancer cells. This review summarizes findings from fundamental research together with clinical data on the use of local anesthetics as anticancer standalone drugs or their combination with conventional treatments. We suggest that a better comprehension of the anticancer effects of local anesthetics at the preclinical and clinical levels may broadly improve the surgical treatment of cancer.