Methotrexate (MTX) is one of the most commonly used drugs in the treatment of inflammatory rheumatic diseases. Unfortunately, MTX is an FDA Pregnancy Category X medication, which means it is contraindicated during pregnancy. The following review of the literature, with international guidelines, gives in addition an overview of current scientific knowledge on the topic. MTX is a teratogenic substance. It accesses the placenta and, for the dosage of 5 to 25 mg per week normally used in rheumatic diseases, can lead to both habitual abortions and anomalies in the neonate. Folic acid antagonism of MTX is the reason. In the rheumatologic setting, small case reports are available for the usage of MTX of 101 pregnant women at the time of conception or during pregnancy, mostly during the first trimester. Individual casuistry also exists. An abortion rate of 23% was found to result from these case reports. The anomaly rate for neonates was >5%. Only a few pregnancies with neonatal anomalies are described with the child's father taking MTX at the time of conception. MTX is taken up (in small amounts) by the mother's milk, and breast feeding under MTX therapy, therefore, is also contraindicated. Detailed and exact information on female patients taking MTX during the reproduction phase, but also for the father-to-be of the child if treated with MTX, with reference to the required contraception until at least three months before a planned conception and stopping of MTX at least at that time, is essential.