Globally, primary toxoplasmosis on gestation generates annually 190,100 new cases of congenital toxoplasmosis with a global burden of 1.20 million DALYs. Although Toxoplasma gondii infection is easily diagnosable and effectively treatable on the mother, out of prenatal screening setting, newborn diagnosis and early treatment might be problematic. In fact, the large majority of infected newborn display normal on clinical examination, with positive IgG of maternal origin and possibly negative IgA and IgM, with the consequence of late treatment on subclinical cases who are the ideal target of long-term pharmacological treatment. Moreover, toxoplasmosis is on the list of neglected disease of poverty. As consequence, the interest of manufacturers shows low, and standard of treatment continues to rely on a not curative and toxic medicine combination. Fortunately, research in progress on Toxoplasma gondii and host genetics and epigenetic machinery, including unusual histone variants and plantlike transcriptional and posttranscriptional motifs, could pave the way to potential new drugs and/or to channel the choice to treat or not to treat (and how long) subclinical onset forms. On the chapter, practical sustain on management at birth and on the long term of infant exposed to maternal Toxoplasma gondii infection or definitely congenitally infected (text, tables, and figure) is updated on the state of the art.