One of the most challenging problems regarding diseases of the abdominal wall is giant hernias, which in most cases have loss of domain (LOD). Loss of domain refers to the impossibility of repairing these hernias, taking the hernia content into the abdominal cavity with no physiological and anatomical detriment. Patients with loss of domain hernias, suffer from psychological, physiological, and anatomical problems, such as low self-esteem, breathing problems, and bowel malfunction. Preoperative imaging, multidisciplinary approach, and adjuvant therapies are the cornerstone to the treatment of loss of domain hernias, thus making it possible to restore the abdominal wall anatomy with minimal side effects. It is important to consider the different surgical techniques available, to offer each patient a tailor-made option to repair their hernia, considering hernia characteristics, patient comorbidities, and surgeon experience. Adjuvant preoperative options such as progressive pneumoperitoneum and botulinum toxin have become widespread practice, as well as surgical techniques such as anterior component separation or transverse abdominal release. Each of these will help in improving the possibility that the patient will have in restoring his/her abdominal wall anatomy, improving their quality of life.