There seems to be little doubt that xenobiotic and plant derived organosulfur compounds have enormous benefits for in vitro cellular functions and for a multitude of diseases, including cancer. Since there are numerous reviews on anticancer activities of plant organosulfurs, the focus herein will be on alterations associated with xenobiotic organosulfurs. Benefits of 2-mercaptoethanol (2-Me), N-Acetyl-cysteine, cysteamine, thioproline, piroxicam, disulfiram, amifostine, sulindac, celecoxib, oltipraz and their derivates on transplanted homologous tumors and on autochthonous cancers with a viral-, radiation-, chemical carcinogen-, and undefined-etiology are assessed. Because all organosulfurs were not tested for activity in each of the etiology categories, comparative evaluations are restricted. In general, all ‘appeared’ to lower the incidence of cancer irrespective of etiology; however, since most of these values were determined at ages much younger than at a natural-end-of-life-age, differences most likely, instead, reflect a delayed initiation and/or a slowed progression of tumorigenesis. The poorest, long-term benefits of early intervention protocols occurred for viral- and chemical carcinogen-induced cancers. In addition, once tumorigenesis was beyond the initiation stage, outcomes of organosulfur therapies were extremely poor, indicating that they will not be of significant value as stand alone treatments. More importantly, except for the lifetime prevention of spontaneous and radiation-induced mammary tumors by daily dietary 2-Me, similar life long prevention of tumorigenesis was not achieved with other xenobiotics or any of nature’s plant organosulfurs. These results raise an interesting question: Is the variability in incidence found for different organosulfurs associated with (a) their structure, (b) the length of the untreated latency period, (c) treatment duration/dose, and/or (d) the etiology-inducing agent?