Multiple pregnancy represents a challenge for obstetrics and also poses significant psychological, social and economic problems. The chances of a successful outcome may be improved by appropriate preventive, diagnostic and management strategies, by the availability of specific skills and experience and by a multidisciplinary approach. In this paper are indicated and discussed, on the basis of current evidences, what can be considered the ten “commandments” in terms of providing optimal care in multiple pregnancies. In particular in this review we focus on the following topics: psychological support and clinical counseling; diagnosis and characterization of chorionicity; management at referral centers; individualization of care; avoidance of most frequent complications; consideration of specific pathologies; evaluation of fetal anatomy; monitoring of fetuses; planning of time and mode of delivery; monitoring of the mother during postpartum.