Since the birth of the first test-tube baby in 1978, assisted fertilization techniques have been performed all over the world to alleviate human infertility. Later on, with the advent of the intra-cytoplasmic sperm injection (ICSI) technique, severe male infertility cases have been successfully solved. ICSI revolutionized most of the biological knowledge on the mechanism of fertilization, giving rise to a serious debate about its long-term safety. Actually, either conventional in vitro fertilization (IVF) or ICSI are considered commonplace in the clinical practice and chosen on the basis of the specific advantages that they offer in improving the live birth rate. Nevertheless, it remains an open question if these procedures increase the risk for woman health, birth defects and congenital anomalies of the children. In this regard, many meta-analysis are actually reporting the follow-up studies of the IVF-conceived babies. In this review we describe: i) the general biological mechanism of the fertilization in order to compare advantage and disadvantages of IVF vs ICSI; ii) the biological risks associated to different assisted fertilization techniques; and iii) a summary of the extensive literature dealing with pregnancy complications and outcome, congenital malformations, tumors and specific syndromes increase in the children conceived by IVF/ICSI. Results show that the major risks for mother and babies health are associated with multiple gestations and their following complications. On the contrary, although a few exceptions, the majority of the studies do not support an absolute increased health risk for the babies conceived by IVF and ICSI.