The care of individuals with disorders/differences of sex development aims to enable affected individuals and their families to have the best quality of life, particularly those born with severe genital ambiguity. Two of the biggest concerns for parents and health professionals are: (1) making a gender assignment and (2) the decisions of whether or not surgery is indicated, and if so, when is best for the patient and parents. These decisions, which can be overwhelming to families, are almost always made in the face of uncertainties. Such decisions must involve the parents, include multidisciplinary contributions, have an underlying principle of full disclosure, and respect familial, philosophical, and cultural values. Assignment as male or female is made with the realization that gender identity cannot be predicted with certainty. Because of the variability among those with the same diagnosis and complexity of phenotype-genotype correlation, the use of algorithms is inappropriate. The goal of this article is to emphasize the need for individualized care to make the best possible decisions for each patient's unique situation.