Treatment of sex hormones deficiencies in men and women is a subject of considerable discussion due in no small measure to safety concerns. In order to appreciate the appropriate balance between potential risk and benefit, it is important to understand the issues at hand. This is particularly true in the case of the use of testosterone in women. To understand the effect of testosterone supplementation in deficient patients, it is useful to review the normal physiology of testosterone in women. An understanding of the impact of testosterone deficiency will further elucidate perspectives on the topic. This paper aims to present a rational consideration of the known and potential adverse effects of testosterone supplementation in women. Areas of concern regarding the use of androgens in women generally fall into three categories: masculinization, cardiovascular effects and cancer risks, but there are a variety of other issues to be borne in mind. Full understanding of these risks in the context of treating females experiencing testosterone deficiency is limited in some cases, and inferences have to be drawn from other areas.