Penetrating keratoplasty in children is a highly challenging and demanding procedure associated with a high risk of graft failure or failure of amblyopia therapy in clear grafts. Nonetheless, keratoplasty remains the surgery of choice for the management of pediatric corneal stromal opacities or edema. Allograft rejection, graft infection, corneal neovascularization, glaucoma, trauma to the anterior segment, vitreous pathology, and additional surgical interventions, especially those related to glaucoma management, are important risk factors. Successful penetrating keratoplasty in children requires careful preoperative evaluation and selection of patients follow-up by well-motivated parents, an expert corneal transplant surgeon, and a devoted pediatric ophthalmologist.