Congenital anomalies occur in 3 % of normal pregnancies [ 1 ]. Therefore, risk assessment of any particular agent during pregnancy needs to take into account this background rate of teratogenicity. For many years, clinicians relied on the FDA risk categories (A, B, C, D, and X) to assess drugs for safety for use in pregnancy. As Briggs, author of the major textbook in this fi eld, points out, these risk assessments are limited because they are "confusing and simplistic" and incorrectly gave the impression that risk increases from category to category [ 2 ]. The FDA is currently considering new labeling for pregnancy risk. The approach this chapter will take is to present the available data on medication safety in pregnancy and lactation and to synthesize the information regarding drug safety.Each pregnant woman has her own view about assuming risk during her pregnancy. For example, some women will avoid any substance that could have potential risk during pregnancy (caffeine, over-the-counter medications, food-additives) while other women will be willing to assume some risk and modify their ingestion of these substances. Similarly, treating physicians have varying tolerance to risk. While one clinician may be willing to prescribe TNF-α blockers during pregnancy, others will be uncomfortable recommending these medications. Therefore, when approaching management decisions of rheumatic diseases during pregnancy, it is helpful for the treating clinician to be aware of both the patient's and their own risk tolerance, in addition to the available medical data. To this end, up-front discussions prior to conception or early in pregnancy regarding what medications may be used safely and comfortably in the case of a disease fl are are ideal.