The neurofibromatoses are autosomal-dominant neurogenetic disorders including neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis. Among them, NF1 is the most common disorder that is characterized by peripheral nerve sheath tumors, café-au-lait spots, freckles of the skin folds, bone dysplasia, external neurofibromas, and scoliosis. Individuals with NF1 can also present language, visuospatial, and attentional difficulties, executive dysfunctions, and poor emotional and social skills. Moreover, it is known that self-esteem in individuals with NF1 is lower than in general population. The present chapter reviews studies which investigated a possible negative impact of NF1 symptomatology on levels of self-esteem in children, adolescents, and adults. Overall, the literature review showed that symptom visibility and learning difficulties can severely affect self-esteem especially during childhood and adolescence. Other factors reducing levels of self-esteem such as concerns about the risk of passing NF1 to heirs, uncertainty of the disease progression, and sexuality-related worries merge in adulthood. For these reasons, multidisciplinary life course intervention strategies are proposed.