Long term treatment with tamoxifen has produced few side effects, which are generally mild. Of the serious ones, all of them except eye toxicity seem to be related to the molecule's intrinsic mildly estrogen-like action, such as, for example, endometrial carcinoma. This property is also responsible for some favorable clinical effects including a lower risk of osteoporosis and cardiovascular disease. Whether tamoxifen causes neoplastic growth in patients who develop resistance to this drug is still controversial. Further prospective clinical studies are therefore needed to investigate such problems and also to evaluate less frequent side effects. Moreover, decisions on the overall duration of hormone therapy should be based on possible side effects as well as on therapeutic response.